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Int J Mol Sci 2022 Jun 20;23(12). Epub 2022 Jun 20.

Department of Biomaterials Science (BK21 FOUR Program) and Life and Industry Convergence Research Institute, College of Natural Resources & LifeScience, Pusan National University, Miryang 50463, Korea.

Complement component 3 (C3) contributes to neurogenesis, neural migration, and synaptic elimination under normal and disease conditions of the brain, even though it has not been studied in the enteric nervous system (ENS). To determine the role of C3 in the regulatory mechanism of ENS during C3 deficiency-induced constipation, the changes in the markers of neuronal and interstitial cells of Cajal (ICCs), the markers for excitatory and inhibitory transmission of ENS, and expression of C3 receptors were analyzed in the mid colon of C3 knockout (KO) mice at 16 weeks of age. Prominent constipation phenotypes, including the decrease in stool parameters, changes in the histological structure, and suppression of mucin secretion, were detected in C3 KO mice compared to wildtype (WT) mice. Read More

Front Immunol 2022 6;13:823121. Epub 2022 Jun 6.

Department of Hematology, Medical Oncology and Pneumology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.

β2-integrins are heterodimeric surface receptors that are expressed specifically by leukocytes and consist of a variable α (CD11a-d) and a common β-subunit (CD18). Functional impairment of CD18, which causes leukocyte adhesion deficiency type-1 results in an immunocompromised state characterized by severe infections, such as invasive pulmonary aspergillosis (IPA). The underlying immune defects have largely been attributed to an impaired migratory and phagocytic activity of polymorphonuclear granulocytes (PMN). Read More

Proc Natl Acad Sci U S A 2022 Jun 13;119(25):e2201129119. Epub 2022 Jun 13.

Division of Genetics, Department of Biology, University of Erlangen, 91058 Erlangen, Germany.

Sialic acids (Sias) on the B cell membrane are involved in cell migration, in the control of the complement system and, as sialic acid-binding immunoglobulin-like lectin (Siglec) ligands, in the regulation of cellular signaling. We studied the role of sialoglycans on B cells in a mouse model with B cell-specific deletion of cytidine monophosphate sialic acid synthase (CMAS), the enzyme essential for the synthesis of sialoglycans. Surprisingly, these mice showed a severe B cell deficiency in secondary lymphoid organs. Read More

Clin Microbiol Infect 2022 May 28. Epub 2022 May 28.

Section of Pediatrics, Department of Health Sciences, University of Florence, Viale Gaetano Pieraccini 24, 50139, Florence, Italy; Immunology and Molecular Microbiology Unit, Meyer Children's Hospital, Viale Gaetano Pieraccini 24, 50139, Florence, Italy.

Background: Pyogenic bacteria are associated with a wide range of clinical manifestation ranging from common and relatively mild respiratory and cutaneous infections to life-threatening localized or systemic infections, such as sepsis and profound abscesses. Despite vaccination and widespread use of effective antibiotic treatment, severe infection is still observed in a subset of affected patients.

Sources: Case series, review and original articles on human genetic susceptibility to pyogenic infections have been examined. Read More

Mol Cancer Ther 2022 May 2. Epub 2022 May 2.

Faron Pharmaceuticals, Turku, Finland.

Clever-1 is a multifunctional type-1 transmembrane protein that plays an important role in immunosuppression against tumors. Clever-1 is highly expressed in a subset of human tumor-associated macrophages and associated with poor survival. In mice, Clever-1 supports tumor growth and metastasis formation, and its deficiency or blockage induces T-cell-dependent killing of cancer cells. Read More

Evid Based Complement Alternat Med 2022 12;2022:3182220. Epub 2022 Apr 12.

Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Intracerebral neuroinflammation, closely related to brain mast cell (MC) activation, performs an integral function in the pathogenic process of postoperative cognitive dysfunction (POCD). In addition to regulating cognitive activities, the alpha-7-nicotinic acetylcholine receptor (7nAChR) engages in the progression of cognitive deficiency. In this research, we aimed to investigate how electroacupuncture (EA) affects the cognitive function in rats after tibial fracture surgery to determine whether the underlying mechanism involves the inhibition of hippocampal MC degranulation via 7nAChR. Read More

Nan Fang Yi Ke Da Xue Xue Bao 2022 Mar;42(3):392-398

Chongqing Key Laboratory of Lipid and Glucose Metabolism, Center for Lipid Research, Chongqing Medical University, Chongqing 400016, China.

Objective: To investigate the effect CD36 deficiency on muscle insulin signaling in mice fed a normal-fat diet and explore the possible mechanism.

Methods: Wild-type (WT) mice and systemic CD36 knockout (CD36) mice with normal feeding for 14 weeks (=12) were subjected to insulin tolerance test (ITT) after intraperitoneal injection with insulin (1 U/kg). Real-time PCR was used to detect the mRNA expressions of insulin receptor (IR), insulin receptor substrate 1/2 (IRS1/2) and protein tyrosine phosphatase 1B (PTP1B), and Western blotting was performed to detect the protein expressions of AKT, IR, IRS1/2 and PTP1B in the muscle tissues of the mice. Read More

Pediatr Infect Dis J 2022 07 7;41(7):575-578. Epub 2022 Jun 7.

From the Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford University Hospitals NHS Foundation Trust, and National Institute for Health Research Oxford Biomedical Research Centre, Oxford, United Kingdom.

Background: A previous study showed that investigation of children with invasive pneumococcal disease (IPD) revealed an immunodeficiency in up to 10% of cases. Following this report, we implemented a protocol to investigate children with IPD, to assess the proportion with an immunodeficiency in our setting.

Methods: We retrospectively identified patients who presented with IPD from January 2015 to November 2020 and collected data from medical records. Read More

Clin Transl Med 2022 04;12(4):e800

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

In hepatocellular carcinoma (HCC), γδ T cells participate in mediating the anti-tumour response and are linked with a positive prognosis. However, these cells can become pro-tumoural in the tumour microenvironment (TME). We aimed to decipher the immune landscape and functional states of HCC-infiltrating γδ T cells to provide fundamental evidence for the adoptive transfer of allogeneic Vδ2 γδ T cells in HCC immunotherapy. Read More

Front Immunol 2022 14;13:770969. Epub 2022 Mar 14.

Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, China.

This study aims to investigate the effects of threonine (Thr) on immunoregulation and of teleost grass carp (). Juveniles (9.53 ± 0. Read More

J Clin Immunol 2022 May 21;42(4):907-909. Epub 2022 Mar 21.

Department of Dental Medicine, Bretonneau Hospital, APHP, Paris, France.

PLoS One 2022 15;17(3):e0264489. Epub 2022 Mar 15.

Department of Neurology, Yale School of Medicine, New Haven, Connecticut, United States of America.

Acetylcholine receptor (AChR) autoantibodies, found in patients with autoimmune myasthenia gravis (MG), can directly contribute to disease pathology through activation of the classical complement pathway. Activation of the complement pathway in autoimmune diseases can lead to a secondary complement deficiency resulting in reduced complement activity, due to consumption, during episodes of disease activity. It is not clear whether complement activity in MG patients associates with measurements of disease activity or the titer of circulating pathogenic AChR autoantibodies. Read More

Biomed Res Int 2022 3;2022:1141280. Epub 2022 Mar 3.

Department of Pediatrics, Abulcasis International University of Health Sciences, Rabat, Morocco.

Leukocyte adhesion deficiency type 1 (LAD1) is a rare autosomal recessive hereditary disorder characterized by recurrent infections, impaired pus formation, delayed wound healing, omphalitis, and delayed separation of the umbilical cord as hallmark features of the disease. It results from mutations in the integrin 2 subunit gene , which encodes the integrin beta chain-2 protein CD18. In this study, we aimed to investigate the case of a five-month-old boy who presented with a clinical phenotype and flow cytometry results suggesting LAD1 disease. Read More

Transl Stroke Res 2022 Mar 8. Epub 2022 Mar 8.

Departments of Neurosurgery & Translational Neuroscience, Barrow Neurological Institute, SJHMC, Dignity Health, Phoenix, AZ, 85086, USA.

Vascular contributions to cognitive impairment and dementia (VCID) secondary to chronic mild-moderate cerebral ischemia underlie a significant percentage of cases of dementia. We previously reported that either genetic deficiency of the complement C3a receptor (C3aR) or its pharmacological inhibition protects against cerebral ischemia in rodents, while others have implicated C3aR in the pathogenesis seen in rodent transgenic models of Alzheimer's disease. In the present study, we evaluated the role of complement C3a-C3aR signaling in the onset and progression of VCID. Read More

Chin Med J (Engl) 2022 Jan 12;135(4):447-455. Epub 2022 Jan 12.

Department of Dermatology, China-Japan Friendship Hospital, Beijing 100029, China.

Background: Systemic lupus erythematosus (SLE) is a complex autoimmune disease, and the mechanism of SLE is yet to be fully elucidated. The aim of this study was to explore the role of two-pore segment channel 2 (TPCN2) in SLE pathogenesis.

Methods: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression of TPCN2 in SLE. Read More

Signal Transduct Target Ther 2022 02 18;7(1):50. Epub 2022 Feb 18.

Department of Rheumatology and Immunology, Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China.

Neuropsychiatric lupus (NPSLE) is a frequent manifestation of systemic lupus erythematosus (SLE) that occurs in 40-90% of SLE patients; however, the underlying mechanisms remain elusive, causing a severe lack of therapeutic targets for this condition. Here, we show that complement-coordinated elimination of synapses participated in NPSLE in MRL/lpr mice, a lupus-prone murine model. We demonstrated that lupus mice developed increased anxiety-like behaviors and persistent phagocytic microglial reactivation before overt peripheral lupus pathology. Read More

Front Immunol 2021 26;12:792813. Epub 2022 Jan 26.

School of Medicine, University of Dundee, Dundee, United Kingdom.

Integrins in effector T cells are crucial for cell adhesion and play a central role in cell-mediated immunity. Leukocyte adhesion deficiency (LAD) type III, a genetic condition that can cause death in early childhood, highlights the importance of integrin/kindlin interactions for immune system function. A TTT/AAA mutation in the cytoplasmic domain of the 2 integrin significantly reduces kindlin-3 binding to the 2 tail, abolishes leukocyte adhesion to intercellular adhesion molecule 1 (ICAM-1), and decreases T cell trafficking . Read More

Sci Rep 2022 02 1;12(1):1700. Epub 2022 Feb 1.

Department of Biomaterials Science (BK21 FOUR Program), College of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang, 50463, Korea.

To determine whether complement component 3 (C3) deficiency affects its receptor downstream-mediated inflammatory response, the current study was undertaken to measure alterations in the inducible nitric oxide synthase (iNOS)‑mediated cyclooxygenase‑2 (COX‑2) induction pathway, inflammasome pathway, nuclear factor-κB (NF-κB) activation, and inflammatory cytokine expressions in the mid colon of C3 knockout (KO) mice. Significant enhancement was observed in expressions of key components of the iNOS‑mediated COX‑2 induction pathway, and in the phosphorylation of mitogen‑activated protein (MAP) kinase members. A similar pattern of increase was also observed in the expression levels of inflammasome proteins in C3 KO mice. Read More

Anticancer Res 2022 Feb;42(2):791-799

Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

Background/aim: We previously observed higher prevalence of high-grade pancreatic intraepithelial neoplasia (PanIN) in LSL-Kras; Pdx1 (KC-Crmp4) mice than LSL-Kras; Pdx1; Crmp4 (KC-Crmp4) mice. This study investigated the relationship between collapsin response mediator protein 4 (CRMP4) and immune cell infiltration in pancreatic cancer.

Materials And Methods: PanIN was induced by intraperitoneal injection of caerulein into KC-Crmp4 and KC-Crmp4 mice, and immune cells in PanIN lesions were compared. Read More

Cell Rep 2022 01;38(3):110259

The Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia; Cellular Genomics Futures Institute, UNSW Sydney, Sydney, NSW, Australia. Electronic address:

CD21 age-associated or atypical memory B cells are autoantibody enriched and poised for plasma cell differentiation. These cells overaccumulate in chronic infections, autoimmune disease, and immunodeficiency, posing the question of what checkpoints normally oppose their accumulation. Here, we reveal a critical role for paralogous calcium-NFAT-regulated transcription factors EGR2 and EGR3 that are induced in self-reactive B cells. Read More

J Invest Dermatol 2022 Jan 7. Epub 2022 Jan 7.

Institute for Systemic Inflammation Research (ISEF), University of Lübeck, Lübeck, Germany. Electronic address:

Epidermolysis bullosa acquisita (EBA) is a rare blistering skin disease induced by autoantibodies directed against type VII collagen (COL7). Transfer of antibodies against murine COL7 (mCOL7) into mice mimics the effector phase of EBA and results in a subepidermal blistering phenotype. Activation of the complement system, and especially the C5a/C5aR1 axis driving neutrophil activation, are critical for EBA pathogenesis. Read More

Cancer Sci 2022 Mar 20;113(3):875-890. Epub 2022 Jan 20.

Cancer Institute, Xuzhou Medical University, Xuzhou, China.

T cells survival, proliferation, and anti-tumor response are closely linked to their mitochondrial health. Complement C1q binding protein (C1QBP) promotes mitochondrial fitness through regulation of mitochondrial metabolism and morphology. However, whether C1QBP regulates T cell survival, proliferation, and anti-tumor immune function remains unclear. Read More

Biomedicines 2021 Dec 16;9(12). Epub 2021 Dec 16.

Irish Centre for Genetic Lung Disease, Department of Medicine, Royal College of Surgeons in Ireland, Beaumont Hospital, D02 YN77 Dublin, Ireland.

Alpha-1 antitrypsin (AAT) deficiency (AATD) is characterized by increased risk for emphysema, chronic obstructive pulmonary disease (COPD), vasculitis, and wound-healing impairment. Neutrophils play a central role in the pathogenesis of AATD. Dysregulated complement activation in AATD results in increased plasma levels of C3d. Read More

Science 2021 Dec 24;374(6575):eabl5450. Epub 2021 Dec 24.

Oral Immunity and Inflammation Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.

Tissue-specific cues are critical for homeostasis at mucosal barriers. Here, we report that the clotting factor fibrin is a critical regulator of neutrophil function at the oral mucosal barrier. We demonstrate that commensal microbiota trigger extravascular fibrin deposition in the oral mucosa. Read More

Sci Immunol 2021 Dec 24;6(66):eabf2489. Epub 2021 Dec 24.

Laboratory of Pathology, National Cancer Institute (NCI), NIH, Bethesda, MD 20892, USA.

While serum-circulating complement destroys invading pathogens, intracellularly active complement, termed the “complosome,” functions as a vital orchestrator of cell-metabolic events underlying T cell effector responses. Whether intracellular complement is also nonredundant for the activity of myeloid immune cells is currently unknown. Here, we show that monocytes and macrophages constitutively express complement component (C) 5 and generate autocrine C5a via formation of an intracellular C5 convertase. Read More

Front Immunol 2021 2;12:607346. Epub 2021 Dec 2.

Center for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan.

C1q/TNF-related proteins (CTRP) including CTRP3 are a group of secreted proteins which have a complement C1q-like domain in common, and play versatile roles in lipid metabolism, inflammation, tumor metastasis and bone metabolism. Previously, we showed that the expression of , encoding CTRP3, is highly augmented in joints of autoimmune arthritis models and CTRP3-deficiency exacerbates collagen-induced arthritis in mice. However, the mechanisms how CTRP3-deficiency exacerbates arthritis still remain to be elucidated. Read More

J Exp Med 2022 02 16;219(2). Epub 2021 Dec 16.

Department of Internal Medicine and Pediatrics, Division of Pediatric Rheumatology, Ghent University Hospital, Ghent, Belgium.

In rare instances, pediatric SARS-CoV-2 infection results in a novel immunodysregulation syndrome termed multisystem inflammatory syndrome in children (MIS-C). We compared MIS-C immunopathology with severe COVID-19 in adults. MIS-C does not result in pneumocyte damage but is associated with vascular endotheliitis and gastrointestinal epithelial injury. Read More

Eur J Dermatol 2021 Oct;31(5):602-608

Department of Dermatology, Peking Union Medical College Hospital, National Clinical Research Center for Dermatologic and Immunologic Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Generalized pustular psoriasis (GPP) is a chronic disease characterized by non-bacterial pustules. Variants in several genes, such as IL36RN, AP1S3, and CARD14, are involved in the pathogenesis of GPP. The prevalence of different gene variants varies among ethnicities, and some variants are related to concurrent psoriasis vulgaris or age at onset. Read More

Nat Commun 2021 12 9;12(1):7172. Epub 2021 Dec 9.

Department of Medicine, University of California San Diego, La Jolla, CA, USA.

Complement receptor of immunoglobulin superfamily (CRIg) is expressed on liver macrophages and directly binds complement component C3b or Gram-positive bacteria to mediate phagocytosis. CRIg plays important roles in several immune-mediated diseases, but it is not clear how its pathogen recognition and phagocytic functions maintain homeostasis and prevent disease. We previously associated cytolysin-positive Enterococcus faecalis with severity of alcohol-related liver disease. Read More

FASEB J 2022 01;36(1):e22080

Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.

Angiogenesis is required in embryonic development and tissue repair in the adult. Vascular endothelial growth factor (VEGF) initiates angiogenesis, and VEGF or its receptor is targeted therapeutically to block pathological angiogenesis. Additional pro-angiogenic cues, such as CXCL12 acting via the CXCR4 receptor, co-operate with VEGF/VEGFR2 to cue vascular patterning. Read More