Publications by authors named "Ping-Chang Yang"

178 Publications

Modulating oxidative stress counteracts specific antigen-induced regulatory T-cell apoptosis in mice.

Eur J Immunol 2021 Apr 3. Epub 2021 Apr 3.

Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen University School of Medicine, Shenzhen, P. R. China.

Treg are known to have a central role in orchestrating immune responses, but less is known about the destiny of Treg after being activated by specific Ags. This study aimed to investigate the role of superoxide dismutase, an active molecule in the regulation of oxidative stress in the body, in the prevention of Treg apoptosis induced by specific Ags. Ag-specific Tregs were isolated from the DO11.10 mouse intestine. A food allergy mouse model was developed with ovalbumin as the specific Ag and here, we observed that exposure to specific Ag induced Treg apoptosis through converting the precursor of TGF-β to its mature form inside the Tregs. Oxidative stress was induced in Tregs upon exposure to specific Ags, in which Smad3 bound the latency-associated peptide to induce its degradation, converting the TGF-β precursor to its mature form, TGF-β. Suppressing oxidative stress in Tregs alleviated the specific Ag-induced Treg apoptosis in in vitro experiments and suppressed experimental food allergy by preventing the specific Ag-induced Treg apoptosis in the intestine. In conclusion, exposure to specific Ags induces Treg apoptosis and it can be prevented by upregulating superoxide dismutase or suppressing reactive oxidative species in Tregs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/eji.202049112DOI Listing
April 2021

Dust mite-derived protein disulfide isomerase suppresses airway allergy by inducing tolerogenic dendritic cells.

J Biol Chem 2021 Mar 23:100585. Epub 2021 Mar 23.

State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University; Shenzhen University School of Medicine, Shenzhen, China. Electronic address:

House dust mites (HDMs) are a potent allergen source that are commonly found in human living environments. While HDMs are known to induce allergic diseases in humans, such as asthma, its other biological activities related to human health are less understood. Our laboratory recently purified the HDM protein PDI (protein disulfide isomerase). In this study, we assess the role of PDI in contributing to immune regulation. Using mass spectrometry, we analyzed the complexes of DEC205 and HDM extracts, and the role of PDI in the induction of tolerogenic dendritic cells (DCs) was assessed in human cell culture experiments and verified in a murine model. We found that that more than 20 HDM-derived proteins, including PDI, bound to DCs by forming complexes with DEC205. Additionally, DEC205-mediated the endocytosis of PDI. HDM-derived PDI (HDM-PDI) promoted Foxp3 expression in DCs. HDM-PDI-primed DCs also showed tolerogenic properties that induced regulatory T cell development, indicating that the primed DCs were tolerogenic DCs. Our results suggested that the PDI/DEC205 /TIEG1/Foxp3 signal pathway activation was involved in the HDM-PDI-induced Foxp3 expression in DCs. Finally, we found that HDM-PDI competitively counteracted the Th2 cytokines to restore DC's tolerogenicity, and administration of HDM-PDI could suppress experimental asthma. In conclusion, our data suggest that HDM-PDI contributes to immune regulation by inducing tolerogenic DC development. Administration of HDM-PDI can alleviate experimental asthma. These findings demonstrate that HDM-PDI has translational potential to be used in the treatment of immune disorders such as asthma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jbc.2021.100585DOI Listing
March 2021

Twist1 sustains the apoptosis resistance in eosinophils in nasal mucosa of allergic rhinitis.

Arch Biochem Biophys 2021 May 16;702:108828. Epub 2021 Mar 16.

Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen, China; Research Center of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China. Electronic address:

Eosinophils (Eos) are the canonical effector cells in allergic rhinitis (AR) and many inflammatory diseases. The mechanism of eosinophilia occurring in the lesion sites is not fully understood yet. Twist1 protein (Twist, in short) is an apoptosis inhibitor that also has immune regulatory functions. This study aims to investigate the role of Twist in the pathogenesis of eosinophilia in AR. In this study, surgically removed human nasal mucosal samples were obtained from patients with chronic sinusitis and nasal polyps with AR (the AR group) or without AR (the nAR group). Eos were isolated from the samples by flow cytometry. We found that abundant Eos were obtained from the surgically removed nasal mucosa tissues of both nAR and AR groups. Significantly higher Ras activation was detected in AR Eos than that in nAR Eos. Ras activation was associated with the apoptosis resistance in AR Eos. The Twist (an apoptosis inhibitor) expression was higher in AR Eos, which was positively correlated with the Ras activation status. The sensitization to IgG induced Twist expression in Eos, in which Ras activated the MAPK-HIF-1α pathway, the latter promoted the Twist gene transcription. Twist bound Rac GTPase activating protein-1 to sustain the Ras activation in Eos. Ras activation sustained the apoptosis resistance in Eos. In conclusion, high Ras activation was detected in the AR nasal mucosal tissue-isolated Eos. IgG-sensitization induced Ras activation and Twist expression in Eos, that conferred Eos the apoptosis resistance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.abb.2021.108828DOI Listing
May 2021

Chimeric antigen-guiding extracellular vesicles eliminate antigen-specific Th2 cells in subjects with food allergy.

World Allergy Organ J 2021 Mar 24;14(3):100522. Epub 2021 Feb 24.

Research Center of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China.

Background: Antigen (Ag)-specific T helper (Th)2 cells play a central role in food allergy (FA) pathogenesis. Methods can be used to eliminate Ag-specific Th2 cells that are currently lacking. This study aims to eliminate the Ag-specific Th2 cells with a novel nanoparticle, the mEV (modified extracellular vesicles, that carry a chimeric antigen peptide, MHC II and caspase 3) in a murine FA model.

Methods: mEVs were generated by exposing dendritic cells (DC) to ovalbumin (OVA, a specific Ag) and recombinant caspase 3 (Casp3) in the culture overnight. Exosomes were purified from culture supernatant by the magnetic antibody approach. A murine FA model was developed with OVA as the specific Ag.

Results: Purified mEVs had the molecular markers of extracellular vesicle, CD81, CD63, and CD9, cleaved Casp3 and MHC II/OVA complexes. mEVs specifically bound to the surface of Ag-specific CD4 T cells, induced Ag-specific CD4 T cell apoptosis both and as well as increased regulatory T cells in the intestinal tissues. Administration of mEV efficiently suppressed experimental FA.

Conclusions: mEVs carry Ag/MHC II complexes and Casp3, that can induce Ag-specific Th2 cell apoptosis. Administration of mEV can efficiently suppress experimental FA. The results suggest that the mEVs have the translational potential to be used in the treatment of FA and other allergic diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.waojou.2021.100522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918277PMC
March 2021

Epithelial cell-derived CD83 restores immune tolerance in the airway mucosa by inducing regulatory T-cell differentiation.

Immunology 2021 Feb 4. Epub 2021 Feb 4.

Research Center of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China.

The mechanism of generation of regulatory T cells (Treg) remains incompletely understood. Recent studies show that CD83 has immune regulatory functions. This study aims to investigate the role of epithelial cell-derived CD83 in the restoration of immune tolerance in the airway mucosa by inducing the Treg differentiation. In this study, CD83 and ovalbumin (OVA)-carrying exosomes were generated from airway epithelial cells. An airway allergy mouse model was developed to test the role of CD83/OVA-carrying exosomes in the suppression of airway allergy by inducing Treg generation. We observed that mouse airway epithelial cells expressed CD83 that could be up-regulated by CD40 ligand. The CD83 deficiency in epithelial cells retarded the Treg generation in the airway mucosa. CD83 up-regulated transforming growth factor-β-inducible early gene 1 expression in CD4 T cells to promote Foxp3 expression. Exposure of primed CD4 T cells to CD83/OVA-carrying exosomes promoted antigen-specific Treg generation. Administration of CD83/OVA-carrying exosomes inhibited experimental airway allergic response. In summary, airway epithelial cells express CD83 that is required in the Treg differentiation in the airway mucosa. Administration of CD83/OVA-carrying exosomes can inhibit airway allergy that has the translation potential in the treatment of airway allergic disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/imm.13317DOI Listing
February 2021

Integrin αvβ6 cooperates with resiquimod to restore antigen-specific immune tolerance in airway allergy.

Immunol Lett 2021 Feb 29;230:49-58. Epub 2020 Dec 29.

Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen, China; Research Center of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China. Electronic address:

Background: Integrin αvβ6 can convert the transforming growth factor (TGF)-β precursor to the mature form. Resiquimod (R848) can generate TGF-β-producing regulatory T cells (Treg). Thus, to concurrent administration of specific antigen and R848 may generate antigen-specific Tregs, that is expected to restore immune tolerance in subjects with airway allergic diseases (AAD).

Methods: A bio-nanoparticle, designated Rexo, containing an antigen/MHC II complex and R848, was naturally assembled in dendritic cells, that was released as an exosome. An AAD mouse model was developed used to test the effects of Rexo on restoring the immune tolerance in the airways.

Results: Exposure to R848 failed to induce Tregs in the β6-deficient mouse airway tissues, that were successfully induced in wild type mice. The results were validated inin vitro experiments. R848 activated the TLR7/MyD88/p38 signal pathway to increase the αvβ6 levels in CD4 T cells, the αvβ6 then converted the TGF-β precursor to its mature form, and thus, induced Treg generation. Administration of Rexo restored the antigen-specific immune tolerance in the airways manifesting efficiently suppressing experimental AAD by inducing antigen-specific Tregs in the airways and inhibiting antigen-specific Th2 response.

Conclusions: Rexos can inhibit experimental AAD via inducing antigen-specific Tregs to restore immune tolerance in the airway tissues, suggesting that Rexos have the translational potential to be used in the treatment of AAD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.imlet.2020.12.011DOI Listing
February 2021

Specific Ag-guiding nano-vaccines attenuate neutrophil-dominant allergic asthma.

Mol Immunol 2021 01 20;129:103-111. Epub 2020 Nov 20.

Guangdong Provincial Key Laboratory of New Drug Screening, State Key Laboratory of Organ Failure Research, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China. Electronic address:

Polymorphonuclear neutrophils (PMN) are one fraction of the major inflammatory cells in allergic asthma (asthma, in short); the role of PMN in the asthma pathogenesis is not fully understood yet. This study aims to investigate the effects of specific Ag-guiding exosomes on suppressing the neutrophil-dominant airway inflammation. In this study, BALB/c mice were immunized with ovalbumin plus complete Freund adjuvant to induce an asthma model featured with neutrophil-dominant lung inflammation. The Ag specific PMN (sPMN)-targeting exosomes (tExo), that were exosomes carrying a complex of specific Ag/anti-CD64 Ab and Fas ligand, were constructed to be used to alleviate neutrophilic asthma in mice. We found that sPMNs were the major cellular component in bronchoalveolar lavage fluid (BALF) in asthma mice, while less than 3% PMNs in naive control mice. The sPMNs expressed higher levels of CD64, which formed complexes with Ag-specific IgG (sIgG). The sIgG/CD64 complex-carrying PMNs could be activated upon exposing to specific Ags. Exposure to tExos induced Ag-specific PMNs apoptosis. Administration of tExos efficiently suppressed experimental asthma. We conclude that a fraction of sPMN was identified in the airway of asthma mice. The sPMNs could be activated upon exposure to specific Ags. tExos could induce sPMNs apoptosis, that show the translational potential in the treatment of asthma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.molimm.2020.11.005DOI Listing
January 2021

Bcl2 like protine-12 (Bcl2L12) facilitates experimental airway allergic inflammation by inducing autocrine eotaxin in eosinophils.

Immunol Lett 2020 Dec 24;228:93-102. Epub 2020 Oct 24.

Department of Otolaryngology, Affiliated Hospital of Jinan University, Guangzhou, China; Department of Otolaryngology, First Affiliated Hospital. Sun Yat-sen University, Guangzhou, China. Electronic address:

Background: The pathogenesis of airway allergic disorders (AAD) needs to be further investigated. Eosinophils (Eos) are the canonical effector cells in AAD attacks. Bcl2 like protein-12 (Bcl2L12) is an apoptosis inhibitor and an immune regulator. Eos have the defects of apoptosis. This study aims to investigate the role of Bcl2L12 in the AAD pathogenesis by regulating Eo activities.

Methods: Human nasal lavage fluids (NLF) and mouse bronchoalveolar lavage fluids (BALF) was collected. Eos in NLF and BALF were analyzed by flow cytometry. A murine AAD model was developed with ovalbumin as a specific antigen.

Results: We found that Eos isolated from NLF or BALF of AAD subjects expressed high levels of Bcl2L12 and showed defects of apoptosis. The Bcl2L12 expression in Eos was positively correlated with the AAD response. High lipopolysaccharide levels were detected in the AAD airways, that promoted the Bcl2L12 expression in Eos. Bcl2L12 mediated the LPS-induced autocrine eotaxin 1 expression in Eos through activating the MAPK p38/STAT6/NF-κB signal pathway. Depletion of Bcl2L12 in Eos suppressed experimental AAD in mice.

Conclusions: AAD Eos express high levels of Bcl2L12, the latter is associated with AAD response by regulating the autocrine eotaxin 1 in Eos. Depletion of Bcl2L12 in Eos attenuates experimental AAD, suggesting that to suppress the Bcl2L12 Eos has the translational potential in the treatment of AAD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.imlet.2020.10.007DOI Listing
December 2020

Retinoblastoma cell-derived Twist protein promotes regulatory T cell development.

Cancer Immunol Immunother 2021 Apr 27;70(4):1037-1048. Epub 2020 Oct 27.

Department of Otolaryngology, Head and Neck Surgery, Shenzhen Secondary Hospital and First Affiliated Hospital of Shenzhen University, Shenzhen, China.

Background: The development of tumor tissue-infiltrating regulatory T cell (Treg) is incompletely understood. This study investigates the role of retinoblastoma cell (Rbc)-derived Twist‑related protein 1 (Twist) in the Treg development.

Methods: The surgically removed Rb tissues were collected. Rbcs were cultured with CD4 T cells to assess the role of Rbc-derived Twist in the Treg generation.

Results: We found that more than 90% Rbcs expressed Twist. Foxp3 Tregs were detected in the Rb tissues that were positively correlated with the Twist expression in Rbcs, negatively associated with Rb patient survival and sight survival. Treating Rbcs with hypoxia promoted the Twist expression that could be detected in the cytoplasm, nuclei and on the cell surface. Twist activated CD4 T cells by binding the TLR4/myeloid differentiation factor 2 complex and promoted the transforming growth factor-β-inducible early gene 1 product and Foxp3 expression. These Rbc-induced Foxp3 Tregs showed immune-suppressive function on CD8 T cell proliferation.

Conclusions: Rbcs express Twist, that induces IL-4 Foxp3 Tregs; the latter can inhibit CD8 cytotoxic T cell activities. Therefore, Twist may play an important role in the pathogenesis of Rb.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00262-020-02744-zDOI Listing
April 2021

FcγRI plays a critical role in patients with ulcerative colitis relapse.

Eur J Immunol 2021 02 16;51(2):459-470. Epub 2020 Nov 16.

Research Center of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China.

Ulcerative colitis (UC) is a disease that frequently relapses and affects more than 0.1% general population; the underlying mechanism is poorly understood. Published data show that polymorphonuclear neutrophils (PMN) contribute to the pathogenesis of UC. This study aims to identify antigen (Ag)-specific PMNs and investigate their role in UC relapse. In this study, the correlation between PMN activities and UC relapse was assessed in a group of UC patients. A UC mouse model was developed to expand the findings of UC patient study. The results showed that a positive correlation was detected between the high PMN activities and the food Ag-specific IgG amounts in colon biopsies of UC patients. UC patient-derived Ag-specific PMNs could be activated upon exposure to food specific Ag. The Ag/FcγRI complexes were detected on the surface of PMNs in UC patients. Re-exposure of sensitized PMNs to specific Ag triggered PMN activation and induced UC-like inflammation in the mouse colon. We conclude that FcγRI plays a critical role in UC relapse. Inhibition of FcγRI can efficiently inhibits experimental UC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/eji.202048622DOI Listing
February 2021

Inhibition of Bcl2L12 Attenuates Eosinophilia-Related Inflammation in the Heart.

Front Immunol 2020 11;11:1955. Epub 2020 Sep 11.

State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

The eosinophilic inflammation plays a critical role in myocarditis (Mcd); its underlying mechanism remains to be further elucidated. This study aims to investigate the role of Bcl2-like protein 12 (Bcl2L12) in inducing the defects of apoptosis in eosinophils (Eos) of the heart tissues. Human explant heart samples were collected. Eosinophilia and myocarditis (Mcd)-like inflammation were induced in the mouse heart by immunizing with murine cardiac α-myosin heavy chain (MyHCα) peptides. Markedly more Eos were observed in heart tissues from patients with Mcd than those from patients with dilated cardiomyopathy. Eos isolated from Mcd hearts showed the signs of apoptosis defects. The Eo counts in the Mcd heart tissues were positively correlated with the Bcl2L12 expression in Eos isolated from the heart tissues. Exposure to interleukin 5 in the culture induced the expression of Bcl2L12 in Eos. Bcl2L12 bound c-Myc, the transcription factor of Fas ligand (FasL), to prevent c-Myc from binding to the FasL promoter, to restrict the FasL gene transcription in Eos. Inhibition of Bcl2L12 prevented the induction of eosinophilia and Mcd-like inflammation in the mouse heart. The Bcl2L12 expression contributes to apoptosis defects in Eos of the Mcd heart. Blocking Bcl2L12 prevents the eosinophilia induction and alleviates Mcd-like inflammation in mice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2020.01955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516035PMC
April 2021

Cold stress promotes IL-33 expression in intestinal epithelial cells to facilitate food allergy development.

Cytokine 2020 Dec 22;136:155295. Epub 2020 Sep 22.

Department of Allergy, Longgang ENT Hospital and Shenzhen ENT Institute, Shenzhen, China; Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen, China. Electronic address:

Background: The causative factors and pathogenesis of food allergy (FA) is not fully understood yet. Cold stress (CS) occurs frequently in human life that influences physiological activities in the body. In this study, we aimed to investigate the chronic CS (CS) effects on promoting the expression of IL-33 in intestinal epithelial cells.

Methods: CS was carried out by placing mice at 4 °C for 1 h daily for 7 consecutive days. We developed a mouse model used to test the effects of CS on the FA development.

Results: We found that, similar to conventional FA mouse model, CS induced the core body temperature to drop markedly in mice, increased intestinal epithelial barrier permeability and facilitated FA development. CS promoted interleukin (IL)-33 expression in intestinal epithelial cells through the adrenocorticotropic hormone (ACTH)/cortisol axis and via inducing the Il33 promoter methylation. CS facilitated the FA development in mice, that could be blocked by depletion of IL-33 expression in intestinal epithelial cells.

Conclusions: CS induces IL-33 expression in intestinal epithelial cells to promote Th2 polarization in the intestinal tissues and facilitates FA development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cyto.2020.155295DOI Listing
December 2020

Cross-reactive antibodies against dust mite-derived enolase induce neutrophilic airway inflammation.

Eur Respir J 2021 Jan 28;57(1). Epub 2021 Jan 28.

State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen University School of Medicine, Shenzhen, China.

Background And Aims: Neutrophilic inflammation is a hallmark of some specific asthma phenotypes; its aetiology is not yet fully understood. House dust mite (HDM) is the most common factor in the pathogenesis of airway inflammation. This study aims to elucidate the role of cross-antibodies against HDM-derived factors in the development of neutrophilic inflammation in the airway.

Methods: Blood samples were collected from asthma patients with chronic neutrophilic asthma for analysis of HDM-specific cross-reactive antibodies. The role of an antibody against HDM-derived enolase (EnoAb) in the impairment of airway epithelial barrier function and induction of airway inflammation was assessed in a cell culture model and an animal model.

Results: High similarity (72%) of the enolase gene sequences was identified between HDM and human. Serum EnoAb was detected in patients with chronic neutrophilic asthma. The EnoAb bound to airway epithelial cells to form complexes with enolase, which activated complement, impaired airway epithelial barrier functions and induced neutrophilic inflammation in the airway tissues.

Conclusions: HDM-derived enolase can induce specific cross-antibodies in humans, which induce neutrophilic inflammation in the airway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1183/13993003.02375-2019DOI Listing
January 2021

Enolase-specific cross antibodies induce neutrophilic inflammation in the intestine.

J Leukoc Biol 2021 03 18;109(3):633-644. Epub 2020 Aug 18.

Research Center of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China.

The pathogenesis of ulcerative colitis (UC) is to be further investigated. House dust mites (HDM) are highly associated with the pathogenesis of immune inflammation in the body. This study aims to investigate the role of enolase (one of the HDM-derived proteins)-specific cross Abs in the induction of UC-like inflammation. The enolase specific IgG (EsIgG) was identified in UC patients by mass spectrometry. Mice were treated with EsIgG to induce inflammation in the colon mucosa. EsIgG was detected in the serum and the colon tissues of UC patients, which was positively correlated with the polymorphonuclear neutrophil (PMN) counts in the blood and colon tissues of UC patients. EsIgG formed immune complexes with the constitutive enolase in the UC colon epithelium that activated complement, induced epithelial cell apoptosis, compromised epithelial barrier functions, and resulted in UC-like inflammation in the mouse colon. In summary, UC patients have high serum levels of Abs against HDM-derived enolase and intestinal epithelial cell-derived enolase. These Abs attack the colonic epithelium to induce UC-like inflammation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/JLB.3A0620-128RDOI Listing
March 2021

House Dust Mite Specific Antibodies induce Neutrophilic Inflammation in the Heart.

Theranostics 2020 9;10(19):8807-8817. Epub 2020 Jul 9.

State Key Laboratory of Cardiovascular Diseases, Beijing Fuwai Hospital, Beijing, China.

: Inflammatory heart disorders are among the causes of human death. The causative factors of heart inflammation are to be further elucidated. House dust mite (HDM)-derived protein antigens are involved in the pathogenesis of many human diseases. This study aims to investigate the role of HDM-specific autoantibodies in the pathogenesis of heart inflammation. : Human heart tissue samples were obtained from surgically removed hearts in heart transplantation. The interaction of the heart tissues with HDM-specific antibodies was assessed by pertinent immune analysis. The role of HDM-specific autoantibodies in the induction of heart inflammation was assessed with a murine model. : HDM-specific IgG (mIgG) was detected in the serum of patients with myocarditis (Mcd); the mIgG titers were positively correlated with the neutrophil counts in the heart tissues. The mIgG specifically bound to keratin-10 (KRT10) in heart vascular endothelial cells and the heart tissue protein extracts. The amounts of C3a, C5a and C5b-9 were increased in the mouse heart tissues after exposing to mIgG. In the presence of the complement-containing serum, mIgG bound cardiovascular epithelial monolayers to impair the barrier functions. Administration of mIgG or HDM induced the Mcd-like inflammation in the heart, in which neutrophils were the dominant cellular components in the infiltration of inflammatory cells. : Mcd patients with neutrophilic inflammation in the heart had higher serum levels of mIgG. The mIgG bound heart endothelial cells to impair the endothelial barrier functions and induce neutrophilic inflammation in the heart.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/thno.47134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392007PMC
July 2020

Period2 gene regulates diurnal changes of nasal symptoms in an allergic rhinitis mouse model.

Int Forum Allergy Rhinol 2020 Nov 1;10(11):1236-1248. Epub 2020 Jul 1.

Shanxi Medical University, Taiyuan, China.

Background: Allergic rhinitis (AR) symptoms exhibit prominent 24-hour variations associated with the biological clock. Although endogenous glucocorticoids synchronize circadian oscillator in the nasal mucosa, the precise mechanism of AR remains unclear. Therefore, using a mouse model, we investigated the association between circadian-clock genes and AR symptoms at various time-points.

Methods: Based on the rhythmic secretion of corticosterone levels, we chose 2 time-points, ZT4 (10:00 AM) and ZT16 (10:00 PM), to observe dynamic changes of nasal symptoms, immunologic responses, and circadian-clock gene period (Per) expressions.

Results: In the AR group, nasal symptom scores at ZT4 were significantly higher than at ZT16, with a greater increase in eosinophils, mast cells, and total immunoglobulin E levels at ZT4. The scores had a negative correlation with fluctuation of corticosterone levels. T-helper 1 (Th1) cell counts and interferon-γ levels decreased significantly at ZT4 compared with ZT16 in the AR group, whereas Th2 cells; Th17 cells; and interleukin (IL)-4, -13, and -17A levels increased significantly at ZT4 compared with ZT16. Furthermore, Per2 gene expression levels were attenuated at ZT4 and elevated at ZT16, but correlated negatively with Th2 and Th17 responses associated with Gata3 and Rorγt expression levels that were enhanced at ZT4 and reduced at ZT16 in the AR group.

Conclusion: Our results suggest that the Per2 gene may influence diurnal variations of AR symptom severity, partially through its possible anti-inflammatory effect on the circadian regulation of GATA3 and RORγt levels in immune cells. This further demonstrates the neural-immune-endocrinal mechanism of circadian rhythm in AR and sheds new light on chronotherapeutic approaches to AR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/alr.22607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689743PMC
November 2020

Role of FcRI in Antigen-Dependent Eosinophil Activation in Patients With Allergic Rhinitis.

Am J Rhinol Allergy 2021 Jan 25;35(1):86-97. Epub 2020 Jun 25.

Research Center of Allergy & Immunology, 47890Shenzhen University School of Medicine, Shenzhen, China.

Background: The eosinophil (Eo) activation is a crucial factor evoking allergic rhinitis (AR) attacks; factors; the mechanism of triggering Eo activation remains to be further investigated. The interaction of antigen (Ag) and antibody plays a critical role in evoking allergy attacks. This study aims to elucidate the role of FcγRI, the high affinity receptor of IgG, in the Ag-mediated Eo activation.

Methods: Nasal lavage fluids (NLF) were collected from AR patients and healthy control (HC) subjects. Eos were isolated by flow cytometry cell sorting and analyzed by pertinent immunological approaches.

Results: Eos composed more than 60% of the cellular components in AR NLF. Exposure to specific Ags (sAgs) in the culture triggered Eos to release inflammatory mediators. High levels of FcγRI were detected on the surface of AR NLF Eos. Exposure to lipopolysaccharide markedly increased the FcγRI expression in naive Eos, which could be bound by Ag-specific IgG (sIgG) to form complexes on the surface of Eos; this made Eos at the sensitized status. Eos bore with the sIgG/FcγRI complexes could be activated upon exposure to sIgG in the culture; these Eos can be designated as Ag-specific Eos. Passive transfer of Ag-specific Eos resulted in profound AR response in mice upon sAg challenge. Depletion of FcγRI on Eos efficiently abolished AR response in mice.

Conclusions: AR Eos express high levels FcγRI, that can be bound by sIgG to make Eos sensitized. Re-exposure to specific Ags can activate the sensitized Eos.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1945892420936587DOI Listing
January 2021

Exosomes carry IL-10 and antigen/MHC II complexes to induce antigen-specific oral tolerance.

Cytokine 2020 09 18;133:155176. Epub 2020 Jun 18.

Research Center of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China; Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen, China. Electronic address:

Background: It is known that the immune tolerance can be naturally established in the intestine, while the mechanism by which the immune tolerance development in the intestine is not fully understood yet. Vasoactive intestinal peptides (VIP) has the immune regulatory functions. This study aims to investigate the role of VIP in the immune tolerance development in the intestine.

Methods: Intestinal epithelial cell (IEC)-derived exosomes were prepared. The exosomes carried IL-10 and antigen/MHC II complexes. VIP-deficient (VIPd) mice and wild type mice were employed to test the role of VIP in the development of immune tolerance in the intestine.

Results: VIPd mice failed to induce type 1 regulatory T cells (Tr1 cells) in the intestine and retarded the establishment of antigen (Ag)-specific immune tolerance. Exposure to VIP in the culture induced IL-10 expression in intestinal epithelial cells (IECs). Exosomes derived from ovalbumin (OVA, used as a specific Ag)/VIP-primed IECs carried IL-10 and OVA/MHC II complexes; these exosomes were designated IL10CARs (IL-10/chimeric antigen receptor-carrying exosomes). IL10CARs could recognize OVA-specific CD4 T cells and converted OVA-specific CD4 T cells to OVA-specific Tr1 cells. Administration of IL10CARs suppressed experimental food allergy.

Conclusions: The data show that IL10CARs are capable of suppressing experimental FA by inducing antigen-specific Tr1 cells, which has the translation potential for FA treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cyto.2020.155176DOI Listing
September 2020

Identification of antigen-specific neutrophils in the tonsils with recurrent acute inflammation.

Autoimmunity 2020 08 11;53(5):237-244. Epub 2020 Jun 11.

Research Center of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China.

The pathogenesis of recurrent acute tonsillitis (Rtn) is to be further investigated. Polymorphonuclear neutrophils (PMN) often associate with the pathogenesis of acute and chronic inflammation. This study aims to identify the antigen-specific PMNs (sPMNs) isolated from the tonsillar tissues with recurrent acute inflammation. In this study, CD66b PMNs were isolated from surgically removed tonsils (40 tonsils were from 20 Rtn patients; 24 tonsils were from 12 tonsil tumour patients) by flow cytometry cell sorting. sPMNs were identified through immunological approaches. We found that compared with the control tonsil samples (from marginal non-tumour tissues of tonsil cancer), Rtn samples showed higher PMN frequency, higher levels of myeloperoxidase (MPO) and neutrophil elastase (NE), in which positive correlation was detected between the inflammatory scores in the Rtn tissues and PMN counts ( = .7352;  = .0002), or MPO ( = .6565,  = .0017), or NE ( = .6687,  = .0013). Upon exposure to tonsillar tissue protein extracts in the culture, a portion of Rtn PMNs was activated and released inflammatory mediators. A complex of tonsillar tissue-specific IgG and FcγRI was observed on the surface of Rtn PMNs; these PMNs could specifically recognize the Rtn tissue extracts and were designated the tonsillar antigen-specific PMNs (sPMNs). A signal transduction pathway of mitogen-activated protein kinase (MAPK)-nuclear factor of T cell activation (NFAT) was activated in sPMNs after exposure to Rtn tissue extracts. In summary, a fraction of sPMN in the Rtn tonsillar tissues was identified and characterized. The sPMNs can be activated upon exposure to tonsil-specific antigens. These sPMNs may contribute to the Rtn pathogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/08916934.2020.1777284DOI Listing
August 2020

Single-Cell RNA Sequencing to Dissect the Immunological Network of Autoimmune Myocarditis.

Circulation 2020 Jul 20;142(4):384-400. Epub 2020 May 20.

State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (X.H., Y.C., Y.H., X.C., J.S.).

Background: Myocarditis can develop into dilated cardiomyopathy, which may require heart transplantation. The immunological network of myocarditis phases remains unknown. This study aimed to investigate the immunological network during the transition from myocarditis to cardiomyopathy and to identify the genes contributing to the inflammatory response to myocarditis.

Methods: Mice were treated with myosin heavy chain-α peptides to generate an experimental autoimmune myocarditis (EAM) model. We performed single-cell RNA sequencing analysis of cells extracted from mouse hearts during different EAM phases, including normal control, acute inflammatory, subacute inflammatory, and myopathy phases. Human heart tissues were collected from the surgically removed hearts of patients who had undergone heart transplantation.

Results: We identified 26 cell subtypes among 34 665 cells. Macrophages constituted the main immune cell population at all disease phases (>60%), and an inflammation-associated macrophage cluster was identified in which the expression of -regulated genes was upregulated. The neutrophil population was increased after the induction of EAM, and neutrophils then released to participate in the EAM process. T cells were observed at the highest percentage at the subacute inflammatory phase. T-helper 17 cells, in which the expression of -regulated genes was upregulated, constituted the main T-cell population detected at the acute inflammatory phase, whereas regulatory T cells were the main T-cell population detected at the subacute inflammatory phase, and γδ T cells releasing were the main T-cell population observed at the myopathy phase. Moreover, the expression level correlated with the extent of inflammation. In addition, PX-478 could alleviate the inflammatory responses of the different EAM phases. Last, was expressed at higher levels in patients with acute autoimmune myocarditis than in patients with dilated cardiomyopathy and healthy control subjects.

Conclusions: We present here a comprehensive single-cell landscape of the cardiac immune cells in different EAM phases. In addition, we elucidate the contribution of to the inflammatory response through the regulation of immune cell activity, particularly of macrophage cluster 2 and T-helper 17 cells. Moreover, an inhibitor alleviated inflammatory cell infiltration of the EAM model and may serve as a potential therapeutic target in the clinic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCULATIONAHA.119.043545DOI Listing
July 2020

Specific antigen-guiding exosomes inhibit food allergies by inducing regulatory T cells.

Immunol Cell Biol 2020 09 15;98(8):639-649. Epub 2020 Jul 15.

Research Center of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China.

The therapies for food allergy (FA) need to be improved. The generation of inducible regulatory T cells (Tregs) can support immune tolerance in the body. This study aims to suppress experimental FA by inducing Tregs through the employment of modified exosomes (mExosomes). In this study, mExosomes were prepared by incubating dendritic cells with interleukin (IL)-2 and ovalbumin (OVA, used as a specific antigen) in the culture. Exosomes were purified from culture supernatant and used as the mExosomes. A murine FA model was developed to test the effects of mExosomes on the generation of Tregs in the mouse intestinal tissues and inhibiting FA. The results showed that mExosomes, which carried IL-2 and a complex of OVA peptide-major histocompatibility complex class II on the surface of exosomes, bound to OVA-specific CD4 T cells and induced CD4 T cells to differentiate into Tregs. In the FA mouse intestinal tissues, we found low IL-2 levels that were positively correlated with the number of Tregs. Depletion of IL-2 in mice prevented the generation of Tregs. The levels of peroxisome proliferator-activated receptor-γ were increased in the FA intestinal tissues with inhibited IL-2 production. Administration of mExosomes induced Tregs in the intestinal tissues and efficiently suppressed FA in mice. We conclude that the mExosomes can suppress FA in mice through inducing Tregs. The data suggest that the mExosomes have translational potential in the treatment of FA and other allergic disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/imcb.12347DOI Listing
September 2020

Inhibition of livin overcomes radioresistance in nasopharyngeal carcinoma cells.

PLoS One 2020 2;15(3):e0229272. Epub 2020 Mar 2.

Research Center of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China.

Background And Aims: Radiotherapy is one of the major remedies for the treatment of cancer, including nasopharyngeal carcinoma (NPC). Radioresistance occurs very often in target cells that is a large drawback in cancer treated with radiotherapy. Livin involves the over-growth of cancer cells. This study aims to investigate the role of livin in the radioresistance formation in NPC cells.

Methods: NPC cell lines were exposed to small doses of irradiation to establish a cell model of radioresistance, in which the role of livin in the development of radioresistance was evaluated.

Results: The expression of livin was observed in NPC cells, which was significantly increased after exposing to small doses of irradiation. A negative correlation was detected between livin and Fas expression in NPC cells. Livin formed a complex with heat shock factor-1 (HSF1, the transcription factor of Fas) in NPC cells after irradiation, which sped up ubiquitination of HSF1. Livin was involved in suppressing Fas expression in NPC cells with radioresistance. Exposure to livin inhibitors prevented radioresistance development and overcame the established radioresistance in NPC cells.

Conclusions: Livin expression in NPC cells plays a critical role in the development of radioresistance. Depletion of livin increases the sensitiveness of NPC cells to irradiation. Target therapy against livin may have the translational potential for the treatment of NPC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0229272PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7051067PMC
June 2020

Restoration of Mal overcomes the defects of apoptosis in lung cancer cells.

PLoS One 2020 24;15(1):e0227634. Epub 2020 Jan 24.

ENT Institute, Research Center of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China.

Background And Aims: Cancer is one of the life-threatening diseases of human beings; the pathogenesis of cancer remains to be further investigated. Toll like receptor (TLR) activities are involved in the apoptosis regulation. This study aims to elucidate the role of Mal (MyD88-adapter-like) molecule in the apoptosis regulation of lung cancer (LC) cells.

Methods: The LC tissues were collected from LC patients. LC cells and normal control (NC) cells were isolated from the tissues and analyzed by pertinent biochemical and immunological approaches.

Results: We found that fewer apoptotic LC cells were induced by cisplatin in the culture as compared to NC cells. The expression of Fas ligand (FasL) was lower in LC cells than that in NC cells. FasL mRNA levels declined spontaneously in LC cells. A complex of FasL/TDP-43 was detected in LC cells. LC cells expressed less Mal than NC cells. Activation of Mal by lipopolysaccharide (LPS) increased TDP-43 expression in LC cells. TDP-43 formed a complex with FasL mRNA to prevent FasL mRNA from decay. Reconstitution of Mal or TDP-43 restored the sensitiveness of LC cells to apoptotic inducers.

Conclusions: LC cells express low Mal levels that contributes to FasL mRNA decay through impairing TDP-43 expression. Reconstitution of Mal restores sensitiveness of LC cells to apoptosis inducers that may be a novel therapeutic approach for LC treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0227634PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6980397PMC
April 2020

A20-OVA Nanoparticles Inhibit Allergic Asthma in a Murine Model.

Inflammation 2020 Jun;43(3):953-961

Department of Pediatric Otolaryngology, Shenzhen Hospital, Southern Medical University, 1033 Qinghu Blvd, Shenzhen, 518101, China.

The skewed T helper (Th) 2 response plays a critical role in the pathogenesis of allergic asthma. Regulatory T (Treg) cells and the regulatory cytokines are required in maintaining the homeostasis in the body. This study aims to determine the effects of a poly(lactic-co-glycolic) acid (PLGA)-ovalbumin (OVA)+A20 (a ubiquitin E3 ligase) nanovaccine on inhibiting allergic asthma in a murine model. In this study, A20 and OVA (a model antigen) were encapsulated into PLGA to be a nanovaccine (PLGA-OVA+A20). An allergic asthma murine model was developed with OVA as the specific antigen to test the role of PLGA-OVA+A20 nanovaccine in maintaining the immune homeostasis in the airway tissues. The results showed that PLGA-OVA+A20 nanovaccine inhibited the asthma responses in mice by suppressing Th2 inflammatory responses, promoting the generation of Treg cells in the airway tissues. We conclude that the PLGA-OVA+A20 nanovaccine has a marked inhibitory effect on the airway allergic response in sensitized mice by significantly promoting the generation of Treg cell and IL-10. The data suggest that PLGA-OVA+A20 has translational potential in the treatment of allergic asthma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10753-020-01181-5DOI Listing
June 2020

Soluble CD83 alleviates experimental allergic rhinitis through modulating antigen-specific Th2 cell property.

Int J Biol Sci 2020 1;16(2):216-227. Epub 2020 Jan 1.

Research Center of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China.

: Dysfunction of the immune regulatory system plays a role in the pathogenesis of allergic rhinitis (AR). The underlying mechanism needs to be further investigated. Published data indicate that soluble CD83 (sCD83) has immune regulatory activities. This study aims to investigate the role of sCD83 in the alleviation of experimental AR. : Peripheral blood samples were obtained from AR patients. Serum levels of sCD83 were determined by enzyme-linked immunosorbent assay. A murine AR model was developed to test the effects of sCD83 on suppressing experimental AR. : We found that serum levels of sCD83 in the AR group were lower than that in the healthy control group. A negative correlation was identified between the serum sCD83 levels and the frequency of T helper-2 (Th2) cells. The low serum sCD83 levels were also associated with the Bcl2L12 expression in antigen-specific Th2 cells. Exposure to sCD83 enhanced the responsiveness of antigen-specific Th2 cells to apoptosis inducers via suppressing the Bcl2L12 expression. Administration of sCD83 efficiently suppressed experimental AR. : sCD83 contributes to immune homeostasis by regulating CD4 T cell activities. Administration of sCD83 may have translational potential for the treatment of AR or other allergic diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/ijbs.38722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949156PMC
November 2020

CARsomes inhibit airway allergic inflammation in mice by inducing antigen-specific Th2 cell apoptosis.

Allergy 2020 05 3;75(5):1205-1216. Epub 2020 Feb 3.

ENT Institute of the Research Center of Allergy and Immunology, Shenzhen University School of Medicine, Shenzhen, China.

Background: Skewed T helper (Th)2 response plays a crucial role in the pathogenesis of allergic diseases. The therapeutic efficacy for allergic diseases is unsatisfactory currently. This study aims to regulate the skewed Th2 response with CARsomes.

Methods: The CARsome consisted of an epitope of Dermatophagoides farina-1 (Derf1), a segment of the anti-DEC205 antibody, the scFv, and an open reading frame of perforin. This fusion protein binds to DEC205 molecule on the surface of exosomes derived from dendritic cells (DC). The effects of CARsome on inducing antigen (Ag)-specific Th2 cell apoptosis were assessed both in vivo and in vitro.

Results: Exposure to CARsomes in the culture induced Ag-specific Th2 cell apoptosis. Injection of CARsomes through the vein puncture also induced Ag-specific Th2 cell apoptosis in the lungs of sensitized mice. CARsomes could induce Ag-specific regulatory T cells. Administration of CARsomes efficiently inhibited experimental allergic airway inflammation.

Conclusions: The CARsomes can inhibit allergic airway inflammation by inducing Ag-specific Th2 cell apoptosis and induce Ag-specific regulatory T cells. The data suggest that CARsomes have the translational potential to be used to treat allergic airway inflammation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/all.14157DOI Listing
May 2020

Chimeric specific antigen epitope-carrying dendritic cells induce interleukin-17(+) regulatory T cells to suppress food allergy.

Clin Exp Allergy 2020 02 2;50(2):231-243. Epub 2019 Dec 2.

Research Center of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China.

Background: The on-purpose-modulated dendritic cells (DCs) have shown charming effects on restoring immune regulatory functions in subjects with immune diseases.

Objective: This study aims to construct DCs carrying chimerical antigen (Ag) peptides (CAP-DCs) to induce interleukin (IL)-17+ inducible Tregs (iTregs) to alleviate food allergy (FA) in a murine model.

Methods: In this study, we constructed CAP-DCs. The CAP is a fusion protein, consisting of a segment of recombinant scFv of anti-DEC205 antibody and an ovalbumin (OVA) epitope (IC). A murine OVA-FA model was developed to test the effects of CAP-DCs on suppressing the allergic response in the intestine.

Results: The CAP-DCs are characterized as that a complex of scFv-IC is presented on the surface of the cells, moderately express CD80 and CD86 as well as IL-6, IL-23, transforming growth factor (TGF)-β and CCR9. After being passively transferred with CAP-DCs or injection of scFv-IC, Ag-specific IL-17+ Foxp3+ iTregs were induced in the intestinal lamina propria of FA mice. The iTregs showed immune suppressive effects on Ag-specific Th2 response. FA mice were adoptively transferred with the CAP-DCs or scFv-IC injection, which resulted in a significant decrease in the number of Ag-specific Th2 cells and suppression of FA response in an Ag-specific manner.

Conclusions And Clinical Relevance: CAP-DCs can ameliorate FA response by inducing Ag-specific IL-17+ Foxp3+ iTregs and suppressing Ag-specific Th2 response. To generate CAP-DCs has the translational potential in the treatment of FA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cea.13528DOI Listing
February 2020

Probiotic extracts ameliorate nasal allergy by inducing interleukin-35-producing dendritic cells in mice.

Int Forum Allergy Rhinol 2019 11 17;9(11):1289-1296. Epub 2019 Oct 17.

Research Center of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China.

Background: The therapeutic efficacy of allergic rhinitis (AR) needs to be improved. Probiotics have immunoregulatory functions. In this study we evaluated the effects of protein extracts of probiotics in the amelioration of AR.

Methods: Extracts of Bifidobacterium infantis (EBI) were prepared by lysing the live probiotics. AR mice were developed to be used to evaluate the therapeutic efficacy of EBI.

Results: The results show that EBI induced interleukin (IL)-10-producing dendritic cells (DCs) via increasing IL-35 and signal transducer and activator of transcription 3 (STAT3) phosphorylation. IL-10-expressing DCs induced IL-10-producing B cells (B10 cells), with the latter showing immunosuppressive functions. After challenge with specific antigens, AR mice showed sneezing, nasal itch, and increases in serum-specific immunoglobulin E (IgE) and mouse mast cell protease-1; higher levels of T helper 2 (Th2) cytokines (IL-4, 67.17 ± 10.66; IL-5, 62.83 ± 9.70; IL-13, 51.00 ± 6.69, before treatment) in nasal mucosal protein extracts, which were significantly suppressed (IL-4, 27.00 ± 6.66; IL-5, 23.86 ± 4.53; IL-13, 25.67 ± 4.93, after treatment (p < 0.001) by administration with EBI nasal drops.

Conclusion: EBI can suppress AR via inducing B10 cells. Thus, after carrying out required preclinical experiments and tests, EBI has the translational potential to be used in the treatment of AR and other allergic diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/alr.22438DOI Listing
November 2019

Nasal instillation of probiotic extracts inhibits experimental allergic rhinitis.

Immunotherapy 2019 10 3;11(15):1315-1323. Epub 2019 Sep 3.

Affiliated ENT Hospital & Research Center of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, China. Longgang ENT Hospital & Shenzhen ENT Institute, Shenzhen, China.

 Allergic rhinitis (AR) is a common disease. The therapeutic efficacy of AR needs to be improved. This study aims to evaluate the effects of local administration of probiotic extracts on inhibiting experimental AR. Epithelial cells (ECs) were primed by exposing to extracts (CBe) in the culture to upregulate the expression of IL-10. A mouse AR model was developed to assess the therapeutic potential of CBe in AR. CBe markedly induced the expression of IL-10 in ECs. Co-culture of naive B cells with CBe-primed ECs significantly increased IL-10 expression in the B cells (iB10 cells). The iB10 cells showed immune suppressive function in suppressing effector CD4 T-cell proliferation. Treatment with nasal drops containing CBe efficiently inhibited experimental AR in mice. Local administration of CBe can efficiently inhibit experimental AR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2217/imt-2019-0119DOI Listing
October 2019