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Deficiency of Mouse CD4^+CD25^+Foxp3^+ Regulatory T Cells in Xenogeneic Pig Thymus-Grafted Nude Mice Suffering from autoimmune diseases

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Cellular & Molecular Immunology 2008年第5期5卷 325-332页

作者： Baojun Zhang Chenming Sun Yanyan Qu Aijun Zhang Jun Liu Lianjun Zhang Zeqing Niu Yong Zhao Transplantation Biology Research Division State Key Laboratory of Biomembrane and Membrane Biotechnology Institute of Zoology Chinese Academy of Sciences Beijing China China-U.S. Research Center for Life Sciences Chinese Academy of Sciences Beijing China State Key Laboratory of Biomembrane and Membrane Biotechnology Institute of Zoology Chinese Academy of Sciences Datun Road Beijing 100101 China

Xenogeneic thymus transplantation can efficiently induce specific immune tolerance to donor antigens in athymic recipients. However, many nude mice suffer from autoimmune diseases （AID） for over 10 weeks after xenogeneic thymus transplantation. CD4^＋CD25^＋Foxp3^＋ regulatory T （Treg） cells were recently determined to play a pivotal role in keeping immune tolerance in humans and mice. Thus, we investigated this subpopulation of Treg cells in the periphery of pig thymus-grafted nude mice suffering from AID. Our results showed that the expression of Foxp3, CTLA-4 and GITR on mouse CD4^＋CD25^＋ T cells and the ratio of CD4^＋CD25^＋Foxp3^＋ Treg cells to CD4^＋ T cells were significantly decreased in the periphery of pig thymus-grafted nude mice suffering from AID, compared with healthy pig or mouse thymus-grafted nude mice. Furthermore, mouse CD4^＋CD25^＋ T cells in pig thymus-grafted nude mice suffering from AID showed more severe deficiency in immunosuppressive function compared with the counterpart in xenogeneic pig or syngeneic thymus-grafted nude mice without AID. Thus, the decreased frequency, altered phenotype and functional deficiency of mouse CD4^＋CD25^＋ Treg cells in pig thymus-grafted nude mice may contribute to the development of AID in this model.

关键词： regulatory T cell Foxp3 autoimmune disease pig thymus transplantation

Dawn of CAR-T cell therapy in autoimmune diseases

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Chinese Medical Journal 2024年第10期137卷 1140-1150页

作者： Yuxin Liu Minghao Dong Yunhui Chu Luoqi Zhou Yunfan You Xiaowei Pang Sheng Yang Luyang Zhang Lian Chen Lifang Zhu Jun Xiao Wei Wang Chuan Qin Daishi Tian Department of Neurology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430030China Hubei Key Laboratory of Neural Injury and Functional Reconstruction Huazhong University of Science and TechnologyWuhanHubei 430030China

Chimeric antigen receptor(CAR)-T cell therapy has achieved remarkable success in the treatment of hematological *** on the immunomodulatory capability of CAR-T cells,efforts have turned toward exploring their potential in treating autoimmune *** analysis of 210 records from 128 academic journals published by 372 institutions in 40 countries/regions indicates a growing number of publications on CAR-T therapy for autoimmune diseases,covering a range of subtypes such as systemic lupus erythematosus,multiple sclerosis,among ***-T therapy holds promise in mitigating several shortcomings,including the indiscriminate suppression of the immune system by traditional immunosuppressants,and non-sustaining therapeutic levels of monoclonal antibodies due to inherent pharmacokinetic *** persisting and proliferating in vivo,CAR-T cells can offer a tailored and precise *** paper reviewed preclinical experiments and clinical trials involving CAR-T and CAR-related therapies in various autoimmune diseases,incorporating innovations well-studied in the field of hematological tumors,aiming to explore a safe and effective therapeutic option for relapsed/refractory autoimmune diseases.

关键词： CAR-T cell therapy autoimmune disease Immunotherapy Multiple sclerosis Neuromyelitis optica spectrum disorder Systemic lupus erythematosus

Role of vitamin D in immune responses and autoimmune diseases,with emphasis on its role in multiple sclerosis

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Neuroscience Bulletin 2010年第6期26卷 445-454页

作者：张洪亮吴江吉林大学第一医院神经内科长春130021

Vitamin D is a seco-steroid involved in calcium and phosphorus metabolism,and bone formation and mineralization, through binding to a specific nuclear receptor,vitamin D receptor（VDR）.Besides its well-established functions on bone health,multiple lines of evidence have indicated the immunomodulatory roles of vitamin *** D can affect both innate and adaptive immunity,and prevent autoimmune responses *** D regulates the immune responses by suppressing T cell proliferation and modulating macrophage *** studies have shown that vitamin D deficiency is associated with multiple diseases such as rickets and ***,associations between vitamin D and autoimmune diseases have been confirmed in multiple sclerosis（MS）,rheumatoid arthritis（RA）,*** present review mainly summarized the recent findings on the immunomodulatory role of vitamin D in various disorders,with special focus on its role in MS,an autoimmune disease of the nervous system.

关键词： vitamin D autoimmune disease multiple sclerosis

Regulatory B cells in autoimmune diseases

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Cellular & Molecular Immunology 2013年第2期10卷 122-132页

作者： Min Yang Ke Rui Shengjun Wang Liwei Lu Department of Pathology and Center for Infection and Immunology The University of Hong Kong Hong Kong China Department of Immunology School of Medical Science and Laboratory Medicine Jiangsu University Zhenjiang China These authors contributed equally to this work.

B cells are generally considered to be positive regulators of the immune response because of their capability to produce antibodies, including autoantibodies. The production of antibodies facilitates optimal CD4＋ T-cell activation because B cells serve as antigen-presenting cells and exert other modulatory functions in immune responses. However, certain B cells can also negatively regulate the immune response by producing regulatory cytokines and directly interacting with pathogenic T cells via cell-to-cell contact. These types of B Cells are defined as regulatory B （Breg） cells. The regulatory function of Breg cells has been demonstrated in mouse models of inflammation, cancer, transplantation, and particularly in autoimmunity. In this review, we focus on the recent advances that lead to the understanding of the development and function of Breg cells and the implications of B cells in human autoimmune diseases.

关键词： autoimmune disease interleukin-lO regulatory B cells

The complement system and autoimmune diseases

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Chronic diseases and Translational Medicine 2022年第3期8卷 184-190页

作者： Changhao Jia Ying Tan Minghui Zhao Laboratory of Renal disease Department of MedicineRenal DivisionMinistry of Health of ChinaPeking University First HospitalPeking University Institute of NephrologyBeijingChina Peking-Tsinghua Center for Life Sciences BejingChina Centerfor Interdisciplinary Research in Biomedicine Peking UniversityBeijingChina

The complement system plays a key role in the pathogenesis of autoimmune diseases,which usually injures the *** and more studies have shown the pathogenic role and indicated that abnormal activation of the complement system was highly involved in the outbreak of autoimmune *** review mainly introduced recent studies of complement system activation contributing to the pathogenesis of autoimmune diseases,including systemic lupus erythematosus,antiphospholipid syndrome,antineutrophil cytoplasmic antibody-associated vasculitides,and so *** the pathogenic roles of complement activation in various autoimmune diseases will identify potential novel therapeutic targets on complement systems.

关键词： ANCA-associated vasculitides antiphospholipid syndrome autoimmune disease complement systemic lupus erythematosus

Measurement of Serum IgG4 Levels by an Established ELISA System and Its Clinical Applications in autoimmune diseases

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2013年第4期33卷 611-614页

作者：孙玮高荣芬陈雨苏玉莹董凌莉 Department of Stomatology Union HospitalHuazhong University of Science and Technology Department of Rheumatology Tongji HospitalHuazhong University of Science and Technology

Summary： IgG4-related disease （IgG4-RD） is a novel and rare autoimmune disease entity. Elevated serum IgG4 level is strongly suggestive of IgG4-RD. But it is still unknown whether serum IgG4 eleva tion commonly occurs in other autoimmune diseases. In this study, the serum IgG4 levels were detected by an established enzyme-linked immunosorbent assay （ELISA） in a variety of autoimmune diseases including systemic lupus erythematosus （SLE）, Sjogren＇s syndrome （SS）, polymyositis or dermatomy- ositis （PM/DM） and IgG4-RD. To evaluate the reliability of this ELISA system, some of our samples were sent to a lab in Kanazawa Medical University, Japan, and detected by using the nephelometric as-say. The results showed that our findings were consistent with theirs. Moreover, it was found that the serum IgG4 levels were 0.23±0.16 g/L in 53 healthy controls, 0.16±0.15 g/L in 103 SLE patients, 0.22±0.18 g/L in 41 SS patients and 0.40±0.32 g/L in 21 PM/DM patients. No significant difference in the serum IgG4 level was observed among these groups （P〉0.05）. The serum IgG4 levels of two cases of IgG4-RD were 1.63 and 4.65 g/L respectively, and both decreased markedly after treatment with glucocorticoids. These data indicated that this established ELISA system can be used for detecting serum IgG4 levels. Elevated serum IgG4 levels help diagnose IgG4-RD and evaluate the curative effect of this condition rather than other autoimmune diseases.

关键词： IgG4-related disease IgG4 enzyme-linked immunosorbent assay autoimmune disease

In Vitro Biological Activity of Anti-C Ⅱ TA Hammerhead Ribozyme——A Novel Approach for autoimmune diseases

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2003年第4期23卷 335-338页

作者：刘芳邹萍郭荣陆华中范华骅 Institute of Hematology Department of Hematology Department of Blood Engineering

This study investigated the feasibility of using an hammerhead ribozyme against C Ⅱ TA, a major regulator of MHC Ⅱ antigens, to repress the expression of MHC Ⅱ molecules on Hela cells. A hammerhead ribozyme (Rz464) specific to 463-465 GUC triplet of C Ⅱ TA and its target gene were transcribed, then mixed up and incubated in vitro . The cleavage products were analyzed by PAGE and silver staining. Rz464 was then inserted into the pIRES2 EGFP vector (pRz464). Stable transfectants of Hela with pRz464 were tested for class Ⅱ MHC induction by recombinant human interferon gamma (IFN γ). mRNA of C Ⅱ TA was measured by RT PCR. Our results showed that Rz464 could exclusively cleave C Ⅱ TA RNA. When induced with IFN γ, the expression of HLA DR, DP, DQ on pRz464 + Hela was induced, and the mRNA content of C Ⅱ TA decreased too. It is concluded that Rz464 could inhibit C Ⅱ TA and thus the family of genes was regulated by C Ⅱ TA:MHC Ⅱ molecules. These results provided insight into the future application of Rz464 as a new nucleic acid drug against auto immune diseases.

关键词： MHC class Ⅱ transactivator (C Ⅱ TA) hammerhead ribozyme Hela cell line autoimmune disease

Epigenetic regulation of B cells and its role in autoimmune pathogenesis

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Cellular & Molecular Immunology 2022年第11期19卷 1215-1234页

作者： Fan Xiao Ke Rui Xiaofei Shi Haijing Wu Xiaoyan Cai Kathy O.Lui Qianjin Lu Esteban Ballestar Jie Tian Hejian Zou Liwei Lu Department of Pathology Shenzhen Institute of Research and Innovation and Shenzhen HospitalThe University of Hong KongHong KongChongqing International Institute for ImmunologyChongqingChina Institute of Medical Immunology Affiliated Hospital of Jiangsu UniversityZhenjiangChina Department of Rheumatology and Immunology The First Affiliated Hospital and School of MedicineHenan University of Science and TechnologyLuoyangChina Department of Dermatology Second Xiangya HospitalCentral South UniversityHunan Key Laboratory of Medical EpigenomicsChangshaHunanChina Department of Rheumatology Guangzhou First People’s HospitalSchool of MedicineSouth China University of TechnologyGuangzhouChina Department of Chemical Pathology Faculty of MedicinePrince of Wales HospitalThe Chinese University of Hong KongHong KongChina Epigenetics and Immune disease Group Josep Carreras Research InstituteBadalona08916 BarcelonaSpain Epigenetics in Inflammatory and Metabolic diseases Laboratory Health Science CenterEast China Normal UniversityShanghaiChina Department of Rheumatology Huashan HospitalFudan UniversityShanghaiChina Centre for Oncology and Immunology Hong Kong Science ParkHong KongChina

B cells play a pivotal role in the pathogenesis of autoimmune *** previous studies have shown many genetic polymorphisms associated with B-cell activation in patients with various autoimmune disorders,progress in epigenetic research has revealed new mechanisms leading to B-cell *** mechanisms,including those involving histone modifications,DNA methylation,and noncoding RNAs,regulate B-cell responses,and their dysregulation can contribute to the pathogenesis of autoimmune *** with autoimmune diseases show epigenetic alterations that lead to the initiation and perpetuation of autoimmune ***,many clinical and animal model studies have shown the promising potential of epigenetic therapies for *** this review,we present an up-to-date overview of epigenetic mechanisms with a focus on their roles in regulating functional B-cell ***,we discuss epigenetic dysregulation in B cells and highlight its contribution to the development of autoimmune *** on clinical and preclinical evidence,we discuss novel epigenetic biomarkers and therapies for patients with autoimmune disorders.

关键词： B cells Epigenetic regulation autoimmune disease Biomarker Therapy

A novel cytokine consisting of the p40 and EBI3 subunits suppresses experimental autoimmune arthritis via reciprocal regulation of Th17 and Treg cells

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Cellular & Molecular Immunology 2022年第1期19卷 79-91页

作者： Seon-Yeong Lee Su-Jin Moon Young-Mee Moon Hyeon-Beom Seo Jun-Geol Ryu A Ram Lee Chae Rim Lee Da-Som Kim Yang-Mi Her Jeong Won Choi Seung-Ki Kwok Sung-Hwan Park Mi-La Cho The Rheumatism Research Center The Catholic University of KoreaSeoulSouth Korea Division of Rheumatology Department of Internal MedicineSeoul St.Mary’s HospitalCollege of MedicineThe Catholic University of KoreaSeoulSouth Korea Department of Biomedicine&Health Sciences College of MedicineThe Catholic University of KoreaSeoulSouth Korea Department of Medical Lifescience College of MedicineThe Catholic University of KoreaSeoulSouth Korea These author contributed equally:Seon-Yeong Lee Su-Jin MoonYoung-Mee Moon

OBJECTIVE:The interleukin(IL)-12 cytokine family is closely related to the development of T helper cells,which are responsible for autoimmune disease enhancement or ***-12 family members are generally heterodimers and share threeα-subunits(p35,p19,and p28)and twoβ-subunits(p40 and EBI3).However,aβ-sheet p40 homodimer has been shown to exist and antagonize IL-12 and IL-23 signaling ***,we assumed the existence of a p40-EBI3 heterodimer in nature and sought to investigate its role in immune ***:The presence of the p40-EBI3 heterodimer was confirmed by ELISA,immunoprecipitation,and western blotting.A p40-EBI3 vector and p40-EBI3-Fc protein were synthesized to confirm the immunological role of this protein in mice with collageninduced arthritis(CIA).The anti-inflammatory effects of p40-EBI3 were analyzed with regard to clinical,histological,and immune cell-regulating features in mice with ***:Clinical arthritis scores and the expression levels of proinflammatory cytokines(e.g.,IL-17,IL-1β,IL-6,and TNF-α)were significantly attenuated in p40-EBI3-overexpressing and p40-EBI3-Fc-treated mice with CIA compared to vehicle-treated mice with *** joint damage and vessel formation-related gene expression were also reduced by p40-EBI3 heterodimer *** vitro,the p40-EBI3-Fc protein significantly suppressed the differentiation of Th17 cells and reciprocally induced CD4+CD25+Foxp3+(regulatory T)cells.p40-EBI3 also inhibited osteoclast formation in a concentrationdependent ***:In this study,p40-EBI3 ameliorated proinflammatory conditions both in vivo and in *** propose that p40-EBI3 is a novel anti-inflammatory cytokine involved in suppressing the immune response through the expansion of Treg cells and suppression of Th17 cells and osteoclastogenesis.

关键词： cytokine p40-EBI3 Rheumatoid arthritis autoimmune disease regulatory T cell