Publications by authors named "Zhinan Yin"

129 Publications

IL-27 signalling promotes adipocyte thermogenesis and energy expenditure.

Nature 2021 Nov 24. Epub 2021 Nov 24.

Department of Medicine, School of Medicine, Yale University, New Haven, CT, USA.

Thermogenesis in brown and beige adipose tissue has important roles in maintaining body temperature and countering the development of metabolic disorders such as obesity and type 2 diabetes. Although much is known about commitment and activation of brown and beige adipose tissue, its multiple and abundant immunological factors have not been well characterized. Here we define a critical role of IL-27-IL-27Rα signalling in improving thermogenesis, protecting against diet-induced obesity and ameliorating insulin resistance. Mechanistic studies demonstrate that IL-27 directly targets adipocytes, activating p38 MAPK-PGC-1α signalling and stimulating the production of UCP1. Notably, therapeutic administration of IL-27 ameliorated metabolic morbidities in well-established mouse models of obesity. Consistently, individuals with obesity show significantly decreased levels of serum IL-27, which can be restored after bariatric surgery. Collectively, these findings show that IL-27 has an important role in orchestrating metabolic programs, and is a highly promising target for anti-obesity immunotherapy.
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http://dx.doi.org/10.1038/s41586-021-04127-5DOI Listing
November 2021

c-Myc-activated intronic miR-210 and lncRNA MIR210HG synergistically promote the metastasis of gastric cancer.

Cancer Lett 2021 Nov 9. Epub 2021 Nov 9.

Zhuhai Institute of Translational Medicine, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), Jinan University, Zhuhai, 519000, China; The Biomedical Translational Research Institute, Faculty of Medical Science, Jinan University, Guangzhou, 510632, China. Electronic address:

The relationship between microRNA (miRNA) and hosting long non-coding RNA (lncRNA) remains unclear. Here, the expression levels of microRNA-210 (miR-210) and hosting lncRNA MIR210HG are significantly increased and positively correlated in gastric cancer (GC). Gain- and loss-of-function studies demonstrate that miR-210 and MIR210HG synergistically promote the migration and invasion of GC cells in vitro. Furthermore, GC sublines simultaneously expressing miR-210 and MIR210HG display synergistic promotion of lung metastasis in vivo. Mechanistically, MIR210HG interacts with DExH-box helicase 9 (DHX9) to increase DHX9/c-Jun complex's occupancy on the promoter of matrix metallopeptidases (MMPs), and thus promotes migration and invasion of GC cells. Additionally, miR-210 directly suppresses the expression of dopamine receptor D5 (DRD5), serine/threonine kinase 24 (STK24) and MAX network transcriptional repressor (MNT), resulting in enhanced migration and invasion. Finally, MYC proto-oncogene (c-Myc) transactivates miR-210 and MIR210HG. Overexpression of miR-210 or/and MIR210HG can rescue the inhibitory effect on the migration and invasion by silencing c-Myc. Moreover, c-Myc inhibitor significantly decreases lung metastasis of GC in vivo. Collectively, our findings identify a novel mechanism, by which c-Myc-activated miR-210 and MIR210HG synergistically promote the metastasis of GC.
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http://dx.doi.org/10.1016/j.canlet.2021.11.006DOI Listing
November 2021

IL-27 Derived From Macrophages Facilitates IL-15 Production and T Cell Maintenance Following Allergic Hypersensitivity Responses.

Front Immunol 2021 30;12:713304. Epub 2021 Sep 30.

Department of Dermatology, Duke University, Durham, NC, United States.

Crosstalk between T cells, dendritic cells, and macrophages in temporal leukocyte clusters within barrier tissues provides a new concept for T cell activation in the skin. Activated T cells from these leukocyte clusters play critical roles in the efferent phase of allergic contact hypersensitivity (CHS). However, the cytokines driving maintenance and survival of pathogenic T cells during and following CHS remain mostly unknown. Upon epicutaneous allergen challenge, we here report that macrophages produce IL-27 which then induces IL-15 production from epidermal keratinocytes and dermal myeloid cells within leukocyte clusters. In agreement with the known role of IL-15 as a T cell survival factor and growth cytokine, this signaling axis enhances BCL2 and survival of skin T cells. Genetic depletion or pharmacological blockade of IL-27 in CHS mice leads to abrogated epidermal IL-15 production resulting in a decrease in BCL2 expression in T cells and a decline in dermal CD8 T cells and T cell cluster numbers. These findings suggest that the IL-27 pathway is an important cytokine for regulating cutaneous T cell immunity.
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http://dx.doi.org/10.3389/fimmu.2021.713304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8515907PMC
September 2021

Yeast Shells Encapsulating Adjuvant AS04 as an Antigen Delivery System for a Novel Vaccine against .

ACS Appl Mater Interfaces 2021 Sep 17;13(34):40415-40428. Epub 2021 Aug 17.

Zhuhai Institute of Translational Medicine, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), Jinan University, Zhuhai 51900, China.

() infection causes severe zoonotic toxoplasmosis, which threatens the safety of almost one-third of the human population globally. However, there is no effective protective vaccine against human toxoplasmosis. This necessitates anti- vaccine development, which is a main priority of public health. In this study, we optimized the adjuvant system 04 (AS04), a vaccine adjuvant constituted by 3-O-desacyl-4'-monophosphoryl lipid A (a TLR4 agonist) and aluminum salts, by packing it within natural extracts of β-glucan particles (GPs) from to form a GP-AS04 hybrid adjuvant system. Through a simple mixing procedure, we loaded GP-AS04 particles with the total extract (TE) of lysate, forming a novel anti- vaccine GP-AS04-TE. Results indicated that the hybrid adjuvant can efficiently and stably load antigens, mediate antigen delivery, facilitate the dendritic uptake of antigens, boost dendritic cell maturation and stimulation, and increase the secretion of pro-inflammatory cytokines. In the mouse inoculation model, GP-AS04-TE significantly stimulated the function of dendritic cells, induced a very strong TE-specific humoral and cellular immune response, and finally showed a strong and effective protection against toxoplasma chronic and acute infections. This work proves the potential of GP-AS04 for exploitation as a vaccine against a range of pathogens.
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http://dx.doi.org/10.1021/acsami.1c12366DOI Listing
September 2021

Roux-en-Y Gastric Bypass Improved Insulin Resistance via Alteration of the Human Gut Microbiome and Alleviation of Endotoxemia.

Biomed Res Int 2021 12;2021:5554991. Epub 2021 Jul 12.

The First Affiliated Hospital, Jinan University, Guangzhou, China.

Background: Obesity is a main contributing factor for the development of glucose intolerance and type 2 diabetes mellitus (T2D). Roux-en-Y gastric bypass (RYGB) is believed to be one of the most effective treatments to reduce body weight and improve glucose metabolism. In this study, we sought to explore the underlying mechanisms of weight reduction and insulin resistance improvement after RYGB.

Methods: This was a prospective observational study using consecutive samples of 14 obese subjects undergoing bariatric surgery. Main assessments were serum indexes (blood metabolites, glucose-lipid regulating hormones, trimethylamine-N-oxide (TMAO), and lipopolysaccharide-binding protein (LBP), fecal short-chain fatty acids (SCFAs), and gut microbiota. Correlation analysis of the factors changed by RYGB was used to indicate the potential mechanism by which surgery improves insulin resistance.

Results: The subjects showed significant improvement on indices of obesity and insulin resistance and a correlated change of gut microbiota components at 1 month, 3 months, and 6 months post-RYGB operation. In particular, the abundance of a counterobese strain, had gradually increased with the postoperative time. Moreover, these changes were negatively correlated to serum levels of LBP and positively correlated to serum TMAO and fecal SCFAs.

Conclusions: Our findings uncovered links between intestinal microbiota alterations, circulating endotoxemia, and insulin resistance. This suggests that the underlying mechanism of protection of the intestine by RYGB in obesity may be through changing the gut microbiota.
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http://dx.doi.org/10.1155/2021/5554991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294027PMC
September 2021

Loss of fragile site-associated tumor suppressor promotes antitumor immunity via macrophage polarization.

Nat Commun 2021 07 14;12(1):4300. Epub 2021 Jul 14.

Guangdong Province Key Laboratory for Biotechnology Drug Candidates, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, China.

Common fragile sites (CFSs) are specific breakage-prone genomic regions and are present frequently in cancer cells. The (E2-independent) E3 ubiquitin-conjugating enzyme FATS (fragile site-associated tumor suppressor) has antitumor activity in cancer cells, but the function of FATS in immune cells is unknown. Here, we report a function of FATS in tumor development via regulation of tumor immunity. Fats mice show reduced subcutaneous B16 melanoma and H7 pancreatic tumor growth compared with WT controls. The reduced tumor growth in Fats mice is macrophage dependent and is associated with a phenotypic shift of macrophages within the tumor from tumor-promoting M2-like to antitumor M1-like macrophages. In addition, FATS deficiency promotes M1 polarization by stimulating and prolonging NF-κB activation by disrupting NF-κB/IκBα negative feedback loops and indirectly enhances both CD4 T helper type 1 (Th1) and cytotoxic T lymphocyte (CTL) adaptive immune responses to promote tumor regression. Notably, transfer of Fats macrophages protects mice against B16 melanoma. Together, these data suggest that FATS functions as an immune regulator and is a potential target in cancer immunotherapy.
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http://dx.doi.org/10.1038/s41467-021-24610-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280123PMC
July 2021

Pregnancy Induces an Immunological Memory Characterized by Maternal Immune Alterations Through Specific Genes Methylation.

Front Immunol 2021 7;12:686676. Epub 2021 Jun 7.

Institute of Reproductive Health, Center for Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

During pregnancy, the maternal immune system undergoes major adaptive modifications that are necessary for the acceptance and protection of the fetus. It has been postulated that these modifications are temporary and limited to the time of pregnancy. Growing evidence suggests that pregnancy has a long-term impact on maternal health, especially among women with pregnancy complications, such as preeclampsia (PE). In addition, the presence of multiple immunological-associated changes in women that remain long after delivery has been reported. To explain these long-term modifications, we hypothesized that pregnancy induces long-term immunological memory with effects on maternal well-being. To test this hypothesis, we evaluated the immunological phenotype of circulating immune cells in women at least 1 year after a normal pregnancy and after pregnancy complicated by PE. Using multiparameter flow cytometry (FCM) and whole-genome bisulfite sequencing (WGBS), we demonstrate that pregnancy has a long-term effect on the maternal immune cell populations and that this effect differs between normal pregnancy and pregnancy complicated by PE; furthermore, these modifications are due to changes in the maternal methylation status of genes that are associated with T cell and NK cell differentiation and function. We propose the existence of an "immunological memory of pregnancy (IMOP)" as an evolutionary advantage for the success of future pregnancies and the proper adaptation to the microchimeric status established during pregnancy. Our findings demonstrate that the type of immune cell populations modified during pregnancy may have an impact on subsequent pregnancy and future maternal health.
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http://dx.doi.org/10.3389/fimmu.2021.686676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215664PMC
October 2021

Hindering triple negative breast cancer progression by targeting endogenous interleukin-30 requires IFNγ signaling.

Clin Transl Med 2021 02;11(2):e278

Department of Medicine and Sciences of Aging, "G. d'Annunzio" University, Chieti, Italy.

IL30mRNA expression is associated with the TNBC subtype. IL30 boosts proliferation and migration of TNBC cells and reshapes their immunity gene expression profile. The lack of endogenous IL30 hinders TNBC growth and progression and prolongs host survival. TNBC growth inhibition, due to the lack of endogenous IL30, requires INFγ production by T and NK cells.
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http://dx.doi.org/10.1002/ctm2.278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828256PMC
February 2021

Characterization of γδT cells in lung of Plasmodium yoelii-infected C57BL/6 mice.

Malar J 2021 Feb 15;20(1):89. Epub 2021 Feb 15.

Key Laboratory of Immunology, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China.

Background: Malaria has high morbidity and mortality rates in some parts of tropical and subtropical countries. Besides respiratory and metabolic function, lung plays a role in immune system. γδT cells have multiple functions in producing cytokines and chemokines, regulating the immune response by interacting with other cells. It remains unclear about the role of γδT cells in the lung of mice infected by malaria parasites.

Methods: Flow cytometry (FCM) was used to evaluate the frequency of γδT cells and the effects of γδT cells on the phenotype and function of B and T cells in Plasmodium yoelii-infected wild-type (WT) or γδTCR knockout (γδT KO) mice. Haematoxylin-eosin (HE) staining was used to observe the pathological changes in the lungs.

Results: The percentage and absolute number of γδT cells in the lung increased after Plasmodium infection (p < 0.01). More γδT cells were expressing CD80, CD11b, or PD-1 post-infection (p < 0.05), while less γδT cells were expressing CD34, CD62L, and CD127 post-infection (p < 0.05). The percentages of IL-4, IL-5, IL-6, IL-21, IL-1α, and IL-17 γδT cells were increased (p < 0.05), but the percentage of IFN-γ-expressing γδT cells decreased (p < 0.05) post-infection. The pathological changes in the lungs of the infected γδT KO mice were not obvious compared with the infected WT mice. The proportion of CD3 cells and absolute numbers of CD3 cells, CD3 CD4 cells, CD3 CD8 cells decreased in γδT KO infected mice (p < 0.05). γδT KO infected mice exhibited no significant difference in the surface molecular expression of T cells compared with the WT infected mice (p > 0.05). While, the percentage of IFN-γ-expressing CD3 and CD3 CD8 cells increased in γδT KO infected mice (p < 0.05). There was no significant difference in the absolute numbers of the total, CD69, ICOS, and CD80 B cells between the WT infected and γδT KO infected mice (p > 0.05).

Conclusions: The content, phenotype, and function of γδT cells in the lung of C57BL/6 mice were changed after Plasmodium infection. γδT cells contribute to T cell immune response in the progress of Plasmodium infection.
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http://dx.doi.org/10.1186/s12936-021-03619-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885449PMC
February 2021

Age-Related Immune Profile of the T Cell Receptor Repertoire, Thymic Recent Output Function, and miRNAs.

Biomed Res Int 2020 2;2020:5910823. Epub 2020 Dec 2.

Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou 510632, China.

Background: T cell immunity plays a central role in the body's defense system, including maintaining homeostasis and preventing tumorigenesis and viral infection. Immune system functions degenerate with age, leading to immune senescence. Physiologically, immune senescence is characterized by a decrease in T cell receptor diversity, naive T cell deficiency, and alterations in T cell immune-related miRNAs. However, little is known about the characteristics of T cell immunosenescence in Chinese individuals.

Results: A significant decrease in the miR-17, miR-92a, and miR-181a levels in PBMCs was detected with age. The miR-92a and miR-181a levels were upregulated in CBMCs when comparing healthy individuals to group I (0~9 years), whereas miR-17 was downregulated. The sjTREC level in PBMCs was negatively correlated with age, and a sharp decrease in sjTRECs was found between groups I and II (10~19 years). Twenty-four TCR V subfamilies could be detected in most samples, and most displayed polyclonality, while skewed expression of the V subfamilies as well as an increased oligoclonal tendency was found with age. Similarly, the frequencies of the TCR V and V subfamilies decreased with age, and the alteration in clonality appeared to be stable at different ages.

Conclusion: We made the novel observation of T cell immunosenescence with age in Chinese individuals, which may provide information for immune targets to enhance the T cell immune response in immunotherapy settings for elderly patients.
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http://dx.doi.org/10.1155/2020/5910823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732372PMC
June 2021

Controlling Cytokine Storm Is Vital in COVID-19.

Front Immunol 2020 30;11:570993. Epub 2020 Nov 30.

Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Corona virus disease 2019 (COVID-19) has caused a global outbreak and severely posed threat to people's health and social stability. Mounting evidence suggests that immunopathological changes, including diminished lymphocytes and elevated cytokines, are important drivers of disease progression and death in coronavirus infections. Cytokine storm not only limits further spread of virus in the body but also induces secondary tissue damage through the secretion of large amounts of active mediators and inflammatory factors. It has been determined that cytokine storm is a major cause of deaths in COVID-19; therefore, in order to reverse the deterioration of severe and critically ill patients from this disease, the cytokine storm has become a key therapeutic target. Although specific mechanisms of the occurrences of cytokine storms in COVID-19 have not been fully illuminated, hyper-activated innate immune responses, and dysregulation of ACE2 (angiotensin converting enzyme 2) expression and its downstream pathways might provide possibilities. Tailored immunoregulatory therapies have been applied to counteract cytokine storms, such as inhibition of cytokines, corticosteroids, blood purification therapy, and mesenchymal stem cell therapy. This review will summarize advances in the research of cytokine storms induced by COVID-19, as well as potential intervention strategies to control cytokine storms.
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http://dx.doi.org/10.3389/fimmu.2020.570993DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734084PMC
December 2020

Donor γδT Cells Promote GVL Effect and Mitigate aGVHD in Allogeneic Hematopoietic Stem Cell Transplantation.

Front Immunol 2020 16;11:558143. Epub 2020 Oct 16.

Immunology Programme, Life Sciences Institute and Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.

Disease relapse and graft-versus-host disease (GVHD) are the major complications affecting the outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT). While the functions of αβT cells are extensively studied, the role of donor γδT cells in allo-HSCT is less well defined. Using TCRδ donors lacking γδT cells, we demonstrated that donor γδT cells were critical in mediating graft-versus-leukemia (GVL) effect during allo-HSCT. In the absence of donor γδT cells, IFN-γ production by CD8 T cells was severely impaired. Vγ4 subset was the major γδT cell subset mediating the GVL effect , which was partially dependent on IL-17A. Meanwhile, donor γδT cells could mitigate acute GVHD in a murine allo-HSCT model by suppressing CD4 T cell activation and the major γδT cell subset that exerted this protective function was also Vγ4 γδT cells. Therefore, our findings provide evidence that donor γδT cells, especially Vγ4 subset, can enhance GVL effect and mitigate aGVHD during allo-HSCT.
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http://dx.doi.org/10.3389/fimmu.2020.558143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596318PMC
May 2021

Irreversible electroporation plus allogenic Vγ9Vδ2 T cells enhances antitumor effect for locally advanced pancreatic cancer patients.

Signal Transduct Target Ther 2020 10 23;5(1):215. Epub 2020 Oct 23.

Guangdong Provincial Key Laboratory of Proteomics, State Key Laboratory of Organ Failure Research, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.

Immunotherapy has limited efficacy against locally advanced pancreatic cancer (LAPC) due to the presence of an immunosuppressive microenvironment (ISM). Irreversible electroporation (IRE) can not only induce immunogenic cell death, but also alleviate immunosuppression. This study aimed to investigate the antitumor efficacy of IRE plus allogeneic γδ T cells in LAPC patients. A total of 62 patients who met the eligibility criteria were enrolled in this trial, then randomized into two groups (A: n = 30 and B: n = 32). All patients received IRE therapy and after receiving IRE, the group A patients received at least two cycles of γδ T-cell infusion as one course continuously. Group A patients had better survival than group B patients (median OS: 14.5 months vs. 11 months; median PFS: 11 months vs. 8.5 months). Moreover, the group A patients treated with multiple courses of γδ T-cell infusion had longer OS (17 months) than those who received a single course (13.5 months). IRE combined with allogeneic γδ T-cell infusion is a promising strategy to enhance the antitumor efficacy in LAPC patients, yielding extended survival benefits.ClinicalTrials.gov ID: NCT03180437.
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http://dx.doi.org/10.1038/s41392-020-00260-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582168PMC
October 2020

Allogeneic Vγ9Vδ2 T-cell immunotherapy exhibits promising clinical safety and prolongs the survival of patients with late-stage lung or liver cancer.

Cell Mol Immunol 2021 02 16;18(2):427-439. Epub 2020 Sep 16.

Zhuhai Precision Medical Center, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), Jinan University, Zhuhai, 519000, Guangdong, PR China.

Vγ9Vδ2 T cells are promising candidates for cellular tumor immunotherapy. Due to their HLA-independent mode of action, allogeneic Vγ9Vδ2 T cells can be considered for clinical application. To apply allogeneic Vγ9Vδ2 T cells in adoptive immunotherapy, the methodology used to obtain adequate cell numbers with optimal effector function in vitro needs to be optimized, and clinical safety and efficacy also need to be proven. Therefore, we developed a novel formula to improve the expansion of peripheral γδ T cells from healthy donors. Then, we used a humanized mouse model to validate the therapeutic efficacy of expanded γδ T cells in vivo; furthermore, the expanded γδ T cells were adoptively transferred into late-stage liver and lung cancer patients. We found that the expanded cells possessed significantly improved immune effector functions, including proliferation, differentiation, and cancer cell killing, both in vitro and in the humanized mouse model. Furthermore, a phase I clinical trial in 132 late-stage cancer patients with a total of 414 cell infusions unequivocally validated the clinical safety of allogeneic Vγ9Vδ2 T cells. Among these 132 patients, 8 liver cancer patients and 10 lung cancer patients who received ≥5 cell infusions showed greatly prolonged survival, which preliminarily verified the efficacy of allogeneic Vγ9Vδ2 T-cell therapy. Our clinical studies underscore the safety and efficacy of allogeneic Vγ9Vδ2 T-cell immunotherapy, which will inspire further clinical investigations and eventually benefit cancer patients.
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http://dx.doi.org/10.1038/s41423-020-0515-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027668PMC
February 2021

GLS1-mediated glutaminolysis unbridled by MALT1 protease promotes psoriasis pathogenesis.

J Clin Invest 2020 10;130(10):5180-5196

Zhuhai Precision Medical Center, Zhuhai People's Hospital, Jinan University, Zhuhai, Guangdong, China.

Psoriasis is a severe disease associated with the disturbance of metabolism and inflammation, but the molecular mechanisms underlying these aspects of psoriasis pathology are poorly understood. Here, we report that glutaminase 1-mediated (GLS1-mediated) glutaminolysis was aberrantly activated in patients with psoriasis and in psoriasis-like mouse models, which promoted Th17 and γδ T17 (IL-17A-producing γδ T) cell differentiation through enhancement of histone H3 acetylation of the Il17a promoter, thereby contributing to the immune imbalance and development of psoriasis. We further demonstrate that mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) protease was constitutively active in psoriatic CD4+ and γδ T cells, thereby supporting GLS1 expression by stabilizing c-Jun, which directly binds to the GLS1 promoter region. Blocking the activity of either GLS1 or MALT1 protease resolved Th17 and γδ T17 cell differentiation and epidermal hyperplasia in the psoriasis-like mouse models. Finally, IL-17A enhanced GLS1 expression via the MALT1/cJun pathway in keratinocytes, resulting in hyperproliferation of and chemokine production by keratinocytes. Our findings identify the role of the MALT1/cJun/GLS1/glutaminolysis/H3 acetylation/T17 axis in psoriasis pathogenesis and reveal potential therapeutic targets for this disease.
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http://dx.doi.org/10.1172/JCI129269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524468PMC
October 2020

Bibliometrics Analysis of Butyrophilins as Immune Regulators [1992-2019] and Implications for Cancer Prognosis.

Front Immunol 2020 30;11:1187. Epub 2020 Jun 30.

The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, China.

The butyrophilins (BTNs) represent a unique family of immunoglobulin. They were considered to be involved in milk lactation after their discovery in 1981. With the development of research, an increasing number of research revealed that BTNs play important roles in immune regulation [1992-2019]. Our research aimed to summarize the BTN research status and their relationship with lung cancers and breast cancers by bibliometrics and bioinformatics methods. Our results indicate that the researches on immune-regulatory functions of BTNs gradually developed from 1992 to 2006, whereas they increased quickly after 2007. There are international cooperations among 56 countries, of which the United States is the most active one with the highest number of studies as well as highest citations. By coauthorship and cocitation analysis, we showed that Adrian Hayday, who is active in γδ T-cell field, was an active author in BTN publications with average year of 2015 and led a subfield. By keywords co-occurrence analysis, we found that γδ T cell, which is an important cancer immune regulator, is one important hotspot. Finally, we found that several BTN members' expression levels were significantly correlated with prognosis of lung cancer and breast cancer patients. Thus, these BTNs might play immune regulatory effects and could serve as potential biomarkers for cancer.
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http://dx.doi.org/10.3389/fimmu.2020.01187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338374PMC
April 2021

Inflammation is associated with decreased functional connectivity of insula in unmedicated bipolar disorder.

Brain Behav Immun 2020 10 17;89:615-622. Epub 2020 Jul 17.

Medical Imaging Center, First Affiliated Hospital of Jinan University, Guangzhou 510630, China; Institute of Molecular and Functional Imaging, Jinan University, Guangzhou 510630, China. Electronic address:

Background: Systemic inflammation and immune dysregulation have been considered as risk factors in the pathophysiology of mood disorders including bipolar disorder (BD). Previous neuroimaging studies have demonstrated metabolic, structural and functional abnormalities in the insula in BD, proposed that the insula played an important role in BD. We herein aimed to explore neural mechanisms underlying inflammation-induced in the insular subregions functional connectivity (FC) in patients with BD.

Methods: Brain resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired from 41 patients with unmedicated BD II (current episode depressed), 68 healthy controls (HCs). Three pairs of insular seed regions were selected: the bilateral anterior insula (AI), the bilateral middle insula (MI) and the bilateral posterior insula (PI), and calculated the whole-brain FC for each subregion. Additionally, the serum levels of pro-inflammatory cytokines in patients and HCs, including IL-6 and TNF-α, were detected. Then the partial correlation coefficients between the abnormal insular subregions FC values and pro-inflammatory cytokines levels in patients with BD II depression were calculated.

Results: The BD II depression group exhibited decreased FC between the right PI and the left postcentral gyrus, and increased FC between the left AI and the bilateral insula (extended to the right putamen) when compared with the HC group. Moreover, the patients with BD II depression showed higher IL-6 and TNF-α levels than HCs, and IL-6 level was negatively correlated with FC of the right PI to the left postcentral gyrus.

Conclusions: Our results demonstrated that abnormal FC between the bilateral insula, and between the insula and sensorimotor areas in BD. Moreover, disrupted FC between the insula and sensorimotor areas was associated with elevated pro-inflammatory cytokine levels of IL-6 in BD.
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http://dx.doi.org/10.1016/j.bbi.2020.07.004DOI Listing
October 2020

CFTR is a negative regulator of γδ T cell IFN-γ production and antitumor immunity.

Cell Mol Immunol 2021 Aug 15;18(8):1934-1944. Epub 2020 Jul 15.

Zhuhai Precision Medical Center, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), Jinan University, Zhuhai, 519000, Guangdong, China.

CFTR, a chloride channel and ion channel regulator studied mostly in epithelial cells, has been reported to participate in immune regulation and likely affect the risk of cancer development. However, little is known about the effects of CFTR on the differentiation and function of γδ T cells. In this study, we observed that CFTR was functionally expressed on the cell surface of γδ T cells. Genetic deletion and pharmacological inhibition of CFTR both increased IFN-γ release by peripheral γδ T cells and potentiated the cytolytic activity of these cells against tumor cells both in vitro and in vivo. Interestingly, the molecular mechanisms underlying the regulation of γδ T cell IFN-γ production by CFTR were either TCR dependent or related to Ca influx. CFTR was recruited to TCR immunological synapses and attenuated Lck-P38 MAPK-c-Jun signaling. In addition, CFTR was found to modulate TCR-induced Ca influx and membrane potential (V)-induced Ca influx and subsequently regulate the calcineurin-NFATc1 signaling pathway in γδ T cells. Thus, CFTR serves as a negative regulator of IFN-γ production in γδ T cells and the function of these cells in antitumor immunity. Our investigation suggests that modification of the CFTR activity of γδ T cells may be a potential immunotherapeutic strategy for cancer.
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http://dx.doi.org/10.1038/s41423-020-0499-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322328PMC
August 2021

Adjustments of γδ T Cells in the Lung of -Infected C56BL/6 Mice.

Front Immunol 2020 4;11:1045. Epub 2020 Jun 4.

Guangdong Provincial Key Laboratory of Allergy and Clinical Immunology, Sino-French Hoffmann Institute, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Many kinds of lymphocytes are involved in () infection-induced disease. γδ T cells comprise a small number of innate lymphocytes that quickly respond to foreign materials. In this study, the role of γδ T cells in the lung of -infected C56BL/6 mice was investigated. The results demonstrated that infection induces γδ T cell accumulation in the lung, expressing higher levels of CD25, MHCII, CD80, and PDL1, and lower levels of CD127 and CD62L ( < 0.05). The intracellular cytokines staining results illustrated higher percentages of IL-4-, IL-10-, IL-21-, and IL-6-producing γδ T cells and lower percentages of IFN-γ-expressing γδ T cells in the lung of infected mice ( < 0.05). Moreover, the granuloma size in lung tissue was significantly increased in Vδ mice ( < 0.05). In the lung of -infected Vδ mice, both type 1 and type 2 immune responses were decreased significantly ( < 0.05). In addition, the expression of CD80 and CD69 on B cells was decreased significantly ( < 0.05), and the SEA-specific antibody was markedly decreased ( < 0.05) in the blood of infected Vδ mice. In conclusion, this study indicates that γδ T cells could adjust the Th2 dominant immune response in the lung of -infected mice.
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http://dx.doi.org/10.3389/fimmu.2020.01045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7287124PMC
April 2021

Perforin Acts as an Immune Regulator to Prevent the Progression of NAFLD.

Front Immunol 2020 22;11:846. Epub 2020 May 22.

Zhuhai Precision Medical Center, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), Jinan University, Zhuhai, China.

Non-alcoholic fatty liver disease (NAFLD) is one of the main causes of cirrhosis and major risk factors for hepatocellular carcinoma and liver-related death. Despite substantial clinical and basic research, the pathogenesis of obesity-related NAFLD remains poorly understood. In this study, we show that perforin can act as an immune regulator to prevent the progression of NAFLD. Aged perforin-deficient (Prf) mice have increased lipid accumulation in the liver compared to WT mice. With high-fat diet (HFD) challenge, Prf mice have increased liver weight, more severe liver damage, and increased liver inflammation when compared with WT controls. Mechanistic studies revealed that perforin specifically regulates intrinsic IFN-γ production in CD4 T cells, not CD8 T cells. We found that CD4 T cell depletion reduces liver injury and ameliorates the inflammation and metabolic morbidities in Prf mice. Furthermore, improved liver characteristics in HFD Prf and IFN-γR double knockout mice confirmed that IFN-γ is a key factor for mediating perforin regulation of NAFLD progression. Overall, our findings reveal the important regulatory role perforin plays in the progression of obesity-related NAFLD and highlight novel strategies for treating NAFLD.
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http://dx.doi.org/10.3389/fimmu.2020.00846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7256195PMC
March 2021

Roles of mTORC1 and mTORC2 in controlling γδ T1 and γδ T17 differentiation and function.

Cell Death Differ 2020 07 30;27(7):2248-2262. Epub 2020 Jan 30.

The First Affiliated Hospital, Biomedical Translational Research Institute and College of Pharmacy, Jinan University, Guangzhou, 510632, China.

The metabolism-controlled differentiation of αβ T cells has been well documented; however, the role of a metabolism program in γδ T cell differentiation and function has not been clarified. Here, using CD2-cre; mTORC1 Raptor-f/f, and mTORC2 Rictor-f/f mice (KO mice), we found that mTORC1, but not mTORC2, was required for the proliferation and survival of peripheral γδ T cells, especially Vγ4 γδ T cells. Moreover, mTORC1 was essential for both γδ T1 and γδ Τ17 differentiation, whereas mTORC2 was required for γδ T17, but not for γδ Τ1, differentiation. We further studied the underlying molecular mechanisms and found that depletion of mTORC1 resulted in the increased expression of SOCS1, which in turn suppressed the key transcription factor Eomes, consequentially reducing IFN-γ production. Whereas the reduced glycolysis resulted in impaired γδ Τ17 differentiation in Raptor KO γδ T cells. In contrast, mTORC2 potentiated γδ Τ17 induction by suppressing mitochondrial ROS (mitoROS) production. Consistent with their cytokine production profiles, the Raptor KO γδ T cells lost their anti-tumor function both in vitro and in vivo, whereas both Raptor and Rictor KO mice were resistant to imiquimod (IMQ)-induced psoriasis-like skin pathogenesis. In summary, we identified previously unknown functions of mTORC1 and mTORC2 in γδ T cell differentiation and clarified their divergent roles in mediating the activity of γδ T cells in tumors and autoimmunity.
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http://dx.doi.org/10.1038/s41418-020-0500-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7308385PMC
July 2020

Characterization of Immune Dysfunction and Identification of Prognostic Immune-Related Risk Factors in Acute Myeloid Leukemia.

Clin Cancer Res 2020 04 7;26(7):1763-1772. Epub 2020 Jan 7.

Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Purpose: This study aims to provide comprehensive insights into longitudinal immune landscape in acute myeloid leukemia (AML) development and treatment, which may contribute to predict prognosis and guide clinical decisions.

Experimental Design: Periphery blood samples from 79 patients with AML (at diagnosis or/and after chemotherapy or at relapse) and 24 healthy controls were prospectively collected. We performed phenotypic and functional analysis of various lymphocytes through multiparametric flow cytometry and investigated prognostic immune-related risk factors.

Results: Immune defects in AML were reflected in T and natural killer (NK) cells, whereas B-cell function remained unaffected. Both CD8 T and CD4 T cells exhibited features of senescence and exhaustion at diagnosis. NK dysfunction was supported by excessive maturation and downregulation of NKG2D and NKP30. Diseased γδ T cells demonstrated a highly activated or even exhausted state through PD-1 upregulation and NKG2D downregulation. Effective therapeutic response following chemotherapy correlated with T and NK function restoration. Refractory and relapsed patients demonstrated even worse immune impairments, and selective immune signatures apparently correlated clinical outcomes and survival. PD-1 expression in CD8 T cells was independently predictive of poor overall survival and event-free survival.

Conclusions: T-cell senescence and exhaustion, together with impaired NK and γδ T-cell function, are dominant aspects involved in immune dysfunction in AML. Noninvasive immune testing of blood samples could be applied to predict therapeutic reactivity, high risk for relapse, and unfavorable prognosis.
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http://dx.doi.org/10.1158/1078-0432.CCR-19-3003DOI Listing
April 2020

Serum amyloid A exhibits pH dependent antibacterial action and contributes to host defense against cutaneous infection.

J Biol Chem 2020 02 9;295(9):2570-2581. Epub 2019 Dec 9.

Beijing Advanced Innovation Center for Food Nutrition and Human Health, State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China; Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou 511436, China. Electronic address:

Serum amyloid A (SAA), one of the major highly conserved acute-phase proteins in most mammals, is predominantly produced by hepatocytes and also by a variety of cells in extrahepatic tissues. It is well-known that the expression of SAA is sharply increased in bacterial infections. However, the exact physiological function of SAA during bacterial infection remains unclear. Herein, we showed that SAA expression significantly increased in abscesses of cutaneous infected mice, which exert direct antibacterial effects by binding to the bacterial cell surface and disrupting the cell membrane in acidic conditions. Mechanically, SAA disrupts anionic liposomes by spontaneously forming small vesicles or micelles under acidic conditions. Especially, the N-terminal region of SAA is necessary for membrane disruption and bactericidal activity. Furthermore, we found that mice deficient in SAA1/2 were more susceptible to infection by In addition, the expression of SAA in infected skin was regulated by interleukin-6. Taken together, these findings support a key role of the SAA in host defense and may provide a novel therapeutic strategy for cutaneous bacterial infection.
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http://dx.doi.org/10.1074/jbc.RA119.010626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049966PMC
February 2020

A novel small-molecule inhibitor of trefoil factor 3 (TFF3) potentiates MEK1/2 inhibition in lung adenocarcinoma.

Oncogenesis 2019 Nov 4;8(11):65. Epub 2019 Nov 4.

Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.

TFF3 has been identified as a novel biomarker to distinguish between lung adenocarcinoma (ADC) and lung squamous-cell carcinoma (SCC). Herein, we determined the oncogenic functions of TFF3 and demonstrated the potential of pharmacological inhibition of TFF3 in lung ADC using a novel small-molecule inhibitor of TFF3 dimerization (AMPC). Forced expression of TFF3 in lung ADC cells enhanced cell proliferation and survival, increased anchorage-independent growth, cancer stem cell behavior, growth in 3D Matrigel, and cell migration and invasion. In contrast, depleted expression of TFF3 suppressed these cellular functions. Mechanistically, TFF3 exerted its oncogenic function through upregulation of ARAF and hence enhanced downstream activation of MEK1/2 and ERK1/2. Pharmacological inhibition of TFF3 by AMPC, resulted in markedly decreased cell survival, proliferation, 3D growth and foci formation, and impaired tumor growth in a xenograft mouse model. Moreover, the combination of various MEK1/2 inhibitors with AMPC exhibited synergistic inhibitory effects on lung ADC cell growth. In conclusion, this study provides the first evidence that TFF3 is a potent promoter of lung ADC progression. Targeting TFF3 with a novel small-molecule inhibitor alone or in combination with conventional MEK1/2 inhibitors are potential strategies to improve the outcome of lung ADC.
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http://dx.doi.org/10.1038/s41389-019-0173-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6828705PMC
November 2019

ZIKV infection induces robust Th1-like Tfh cell and long-term protective antibody responses in immunocompetent mice.

Nat Commun 2019 08 27;10(1):3859. Epub 2019 Aug 27.

CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.

Induction of long-lived antibody responses during infection or vaccination is often essential for subsequent protection, but the relative contributions of T follicular helper (Tfh) cells and T helper 1 (Th1) cells for induction of antigen specific antibody responses to viruses are unclear. Here, we establish an acute Zika virus (ZIKV) infection model in immunocompetent mice, and show that ZIKV infection elicits robust Th1-like Tfh cell and protective antibody responses. While these Th1-like Tfh cells share phenotypic and transcriptomic profiles with both Tfh and Th1 cells, they also have unique surface markers and gene expression characteristics, and are dependent on T-bet for their development. Th1-like Tfh cells, but not Th1 cells, are essential for class switching of ZIKV-specific IgG2c antibodies and maintenance of long-term neutralizing antibody responses. Our study suggests that specific modulation of the Th1-like Tfh cell response during infection or vaccination may augment the induction of antiviral antibody response to ZIKV and other viruses.
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http://dx.doi.org/10.1038/s41467-019-11754-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6712032PMC
August 2019

Selenium nanoparticles as new strategy to potentiate γδ T cell anti-tumor cytotoxicity through upregulation of tubulin-α acetylation.

Biomaterials 2019 11 13;222:119397. Epub 2019 Aug 13.

Zhuhai Precision Medical Center, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), Jinan University, Zhuhai, 519000, Guangdong, PR China; The Biomedical Translational Research Institute, Faculty of Medical Science, Jinan University, Guangzhou, 510632, Guangdong, PR China. Electronic address:

Immune cell therapy presents a paradigm for the treatment of malignant tumors. Human Vγ9Vδ2 T cells, a subset of peripheral γδ T cells, have been shown to have promising anti-tumor activity. However, new methodology on how to achieve a stronger anti-tumor activity of Vγ9Vδ2 T cells is under continuous investigation. In this work, we used selenium nanoparticles (SeNPs) to strengthen the anti-tumor cytotoxicity of Vγ9Vδ2 T cells. We found SeNPs pretreated γδ T cells had significantly stronger cancer killing and tumor growth inhibition efficacy when compared with γδ T cells alone. Simultaneously, SeNPs pretreatment could significantly upregulate the expression of cytotoxicity related molecules including NKG2D, CD16, and IFN-γ, meanwhile, downregulate PD-1 expression of γδ T cells. Importantly, we observed that SeNPs promoted tubulin acetylation modification in γδ T cells through interaction between microtubule network and lysosomes since the latter is the primary resident station of SeNPs shown by confocal visualization. In conclusion, SeNPs could significantly potentiate anti-tumor cytotoxicity of Vγ9Vδ2 T cells, and both cytotoxicity related molecules and tubulin acetylation were involved in fine-tuning γδ T cell toxicity against cancer cells. Our present work demonstrated a new strategy for further enhancing anti-tumor cytotoxicity of human Vγ9Vδ2 T cells by using SeNPs-based nanotechnology, not gene modification, implicating SeNPs-based nanotechnology had a promising clinical perspective in the γδ T cell immunotherapy for malignant tumors.
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http://dx.doi.org/10.1016/j.biomaterials.2019.119397DOI Listing
November 2019

Targeting Interleukin(IL)-30/IL-27p28 signaling in cancer stem-like cells and host environment synergistically inhibits prostate cancer growth and improves survival.

J Immunother Cancer 2019 07 31;7(1):201. Epub 2019 Jul 31.

Department of Medicine and Sciences of Aging, G. d'Annunzio University of Chieti-Pescara, Via L. Polacchi 11, 66100, Chieti, Italy.

Background: Interleukin(IL)-30/IL-27p28 production by Prostate Cancer (PC) Stem-Like Cells (SLCs) has proven, in murine models, to be critical to tumor onset and progression. In PC patients, IL-30 expression by leukocytes infiltrating PC and draining lymph nodes correlates with advanced disease grade and stage. Here, we set out to dissect the role of host immune cell-derived IL-30 in PC growth and patient outcome.

Methods: PC-SLCs were implanted in wild type (WT) and IL-30 conditional knockout (IL-30KO) mice. Histopathological and cytofluorimetric analyses of murine tumors and lymphoid tissues prompted analyses of patients' PC samples and follow-ups.

Results: Implantation of PC-SLCs in IL-30KO mice, gave rise to slow growing tumors characterized by apoptotic events associated with CD4T lymphocyte infiltrates and lack of CD4Foxp3 T regulatory cells (Tregs). IL-30 knockdown in PC-SLCs reduced cancer cell proliferation, vascularization and intra-tumoral Indoleamine 2,3-Dioxygenase (IDO)CD11bGr-1 myeloid-derived cells (MDCs) and led to a significant delay in tumor growth and increase in survival. IL-30-silenced tumors developed in IL-30KO mice, IL-30tumors, lacked vascular supply and displayed frequent apoptotic cancer cells entrapped by perforinTRAILCD3Tlymphocytes, most of which had a CD4T phenotype, whereas IL-10TGFβFoxp3Tregs were lacking. IL-30 silencing in PC-SLCs prevented lung metastasis in 73% of tumor-bearing WT mice and up to 80% in tumor-bearing IL-30KO mice. In patients with high-grade and locally advanced PC, those with IL-30tumors, showed distinct intra-tumoral cytotoxic granule-associated RNA binding protein (TIA-1)CD4Tlymphocyte infiltrate, rare Foxp3Tregs and a lower biochemical recurrence rate compared to patients with IL-30tumors in which IL-30 is expressed in both tumor cells and infiltrating leukocytes.

Conclusion: The lack of host leukocyte-derived IL-30 inhibits Tregs expansion, promotes intra-tumoral infiltration of CD4T lymphocytes and cancer cell apoptosis. Concomitant lack of MDC influx, obtained by IL-30 silencing in PC-SLCs, boosts cytotoxic T lymphocyte activation and cancer cell apoptosis resulting in a synergistic tumor suppression with the prospective benefit of better survival for patients with advanced disease.
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http://dx.doi.org/10.1186/s40425-019-0668-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6670138PMC
July 2019

Vitamin C promotes the proliferation and effector functions of human γδ T cells.

Cell Mol Immunol 2020 05 6;17(5):462-473. Epub 2019 Jun 6.

Institute of Immunology, Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein Campus Kiel, Kiel, Germany.

γδ T cells are of interest as effector cells for cellular immunotherapy due to their HLA-non-restricted lysis of many different tumor cell types. Potential applications include the adoptive transfer of in vitro-expanded γδ T cells. Therefore, it is important to optimize the culture conditions to enable maximal proliferative and functional activity. Vitamin C (L-ascorbic acid) is an essential vitamin with multiple effects on immune cells. It is a cofactor for several enzymes, has antioxidant activity, and is an epigenetic modifier. Here, we investigated the effects of vitamin C (VC) and its more stable derivative, L-ascorbic acid 2-phosphate (pVC), on the proliferation and effector function of human γδ T cells stimulated with zoledronate (ZOL) or synthetic phosphoantigens (pAgs). VC and pVC did not increase γδ T-cell expansion within ZOL- or pAg-stimulated PBMCs, but increased the proliferation of purified γδ T cells and 14-day-expanded γδ T-cell lines in response to γδ T-cell-specific pAgs. VC reduced the apoptosis of γδ T cells during primary stimulation. While pVC did not prevent activation-induced death of pAg-restimulated γδ T cells, it enhanced the cell cycle progression and cellular expansion. Furthermore, VC and pVC enhanced cytokine production during primary activation, as well as upon pAg restimulation of 14-day-expanded γδ T cells. VC and pVC also increased the oxidative respiration and glycolysis of γδ T cells, but stimulus-dependent differences were observed. The modulatory activity of VC and pVC might help to increase the efficacy of γδ T-cell expansion for adoptive immunotherapy.
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http://dx.doi.org/10.1038/s41423-019-0247-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192840PMC
May 2020

Quantitative assessment of disease markers using the naked eye: point-of-care testing with gas generation-based biosensor immunochromatographic strips.

J Nanobiotechnology 2019 May 17;17(1):67. Epub 2019 May 17.

The First Affiliated Hospital, Biomedical Translational Research Institute and School of Pharmacy and, and Guangdong Province Key Laboratory of Molecular Immunology and Antibody Engineering, Jinan University, Guangzhou, 510632, China.

Background: Immunochromatographic strips (ICSs) are a practical tool commonly used in point-of-care testing (POCT) applications. However, ICSs that are currently available have low sensitivity and require expensive equipment for quantitative analysis. These limitations prohibit their extensive use in areas where medical resources are scarce.

Methods: We developed a novel POCT platform by integrating a gas generation biosensor with [email protected] Core/Shell nanoparticle ([email protected])-based ICSs (G-ICSs). The resulting G-ICSs enabled the convenient and quantitative assessment of a target protein using the naked eye, without the need for auxiliary equipment or complicated computation. To assess this platform, C-reactive protein (CRP), a biomarker commonly used for the diagnosis of acute, infectious diseases was chosen as a proof-of-concept test.

Results: The linear detection range (LDR) of the G-ICSs for CRP was 0.05-6.25 μg/L with a limit of detection (LOD) of 0.041 μg/L. The G-ICSs had higher sensitivity and wider LDR when compared with commonly used AuNPs and fluorescent-based ICSs. When compared with results from a chemiluminescent immunoassay, G-ICS concordance rates for CRP detection in serum samples ranged from 93.72 to 110.99%.

Conclusions: These results demonstrated that G-ICSs have wide applicability in family diagnosis and community medical institutions, especially in areas with poor medical resources.
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http://dx.doi.org/10.1186/s12951-019-0493-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524263PMC
May 2019

Normalization cancer immunotherapy: blocking Siglec-15!

Signal Transduct Target Ther 2019 19;4:10. Epub 2019 Apr 19.

1The First Affiliated Hospital, Biomedical Translational Research Institute, School of Pharmacy, Jinan University, Guangzhou, China.

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http://dx.doi.org/10.1038/s41392-019-0045-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6473001PMC
January 2021
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