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Explosion of autoimmune diseases and the mosaic of old and novel factors

Cellular & Molecular Immunology 2011年第3期8卷 189-192页

作者： Nancy Agmon-Levin zhexiong lian Yehuda Shoenfeld The Zabludowicz Center for Autoimmune Diseases and Department of Medicine B Sheba Medical CenterTel-HashomerIsrael Institute of Immunology and School of Life Sciences University of Science and Technology of ChinaHefeiChina Incumbent of the Laura Schwarz-Kip Chair for Research of Autoimmune Diseases Tel-Aviv University

In recent decades,an enormous effort has been made to elucidate the pathogenesis of autoimmune and autoinflammatory *** is a multifactorial process in which genetic,immunological,environmental and hormonal factors play in concert,together representing what was termed years ago the‘mosaic of autoimmunity’.To date,more than 80 systemic and organ-specific autoimmune diseases have been defined,and their cumulative burden is substantial,both medically and ***,the burden of autoimmune and autoinflammatory diseases is rising,making these diseases a ubiquitous global phenomenon that is predicted to further increase in the coming *** this issue of the journal,additional aspects of autoimmunity are *** dysregulation and loss of self-tolerance are the cornerstones of autoimmunity.

关键词： ASIA autoimmunity vaccines silicone Golf war syndrome

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Experimental evidence on the immunopathogenesis of primary biliary cirrhosis

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Cellular & Molecular Immunology 2010年第1期7卷 1-10页

作者： Carlo Selmi Francesca Meda Anaid Kasangian Pietro Invernizzi Zhigang Tian zhexiong lian Mauro Podda M Eric Gershwin Department of Translational Medicine Universitàdegli Studi di MilanoMilanItaly Department of Medicine IRCCS Istituto Clinico Humanitas RozzanoMilanItaly Divisionof Rheumatology Allergyand Clinical ImmunologyUniversity of California at DavisDavisCAUSA Institute of Immunology University of Science and Technology of ChinaHefeiChina

Primary biliary cirrhosis(PBC)is a chronic cholestatic liver disease for which an autoimmune pathogenesis is supported by clinical and experimental data,including the presence of autoantibodies and autoreactive T *** etiology remains to be determined,yet data suggest that both a susceptible genetic background and unknown environmental factors determine disease *** infectious and chemical candidates have been proposed to trigger the disease in a genetically susceptible host,mostly by molecular *** recently,several murine models have been reported,including genetically determined models as well as models induced by immunization with xenobiotics and bacteria.

关键词： pathogenesis cirrhosis biliary

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Modulation of liver regeneration via myeloid PTEN deficiency

Modulation of liver regeneration via myeloid PTEN deficiency

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第十一届全国免疫学学术大会

作者： Ma Wentao lian zhexiong University of Science and Technology of China

Objectives:Kupffer cells and natural killer(NK)cells are critical for liver ***,the interplay between Kupffer cells and NK cells during the process of liver regeneration is elusive,and the molecular mechanism underlying this process is poorly *** aim was to investigate the functions of phosphatase and tensin homologue on chromosome 10(PTEN)in Kupffer cells in the regulation of liver regeneration.

关键词： Liver regeneration PTEN Kupffer cell NK cell

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A Mouse Model of Autoimmune Cholangitis via Syngeneic Bile Duct Protein Immunization

A Mouse Model of Autoimmune Cholangitis via Syngeneic Bile D...

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第十二届全国免疫学学术大会

作者： Liu Qingzhi lian zhexiong University of Science and Technology of China South China University of Technology

Backgroud:Primary biliary cholangitis(PBC)is an autoimmune liver disease characterized by the destruction of interlobular biliary ductules,which progressively leads to cholestasis,hepatic fibrosis,cirrhosis,and eventu... 详细信息

关键词： Primary biliary cholangitis bile duct protein T cell

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Characterization of organ-specific regulatory B cells using single-cell RNA sequencing

Characterization of organ-specific regulatory B cells using ...

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第十四届全国免疫学学术大会

作者： Siyu Yang zhexiong lian Chronic Disease Laboratory School of Medicine South China University of Technology

Regulatory B cells(Breg) are considered as immunosuppressive cells. Different subsets of Breg cells have been identified both in human beings and mice. However, there is a lack of unique markers to identify Breg cells, and the heterogeneity of Breg cells in different organs needs to be further illuminated. In this study, we performed high-throughput single-cell RNA sequencing(scRNA-seq) and single-cell B cell receptor sequencing(scBCR-seq) of B cells from murine spleen, liver, mesenteric lymph nodes, bone marrow and peritoneal cavity to better define the phenotype of these cells. Breg cells were identified based on the expression of immunosuppressive genes and IL-10 producing B(B10) cell related genes, to define B10 and non-B10 subsets in Breg cells based on the score of the B10 gene signatures. Moreover, we characterized 19 common genes significantly expressed in Breg cells, including Fcrl5, Zbtb20, Ccdc28b, Cd9, Ptpn22, and further analyzed the transcription factor activity in defined Breg cells. Last, a BCR analysis was used to determine the clonally expanded clusters and the relationship of Breg cells across different organs. We demonstrated that Atf3 may potentially modulate the function of Breg cells as a transcription factor and that 7 organ-specific subsets of Breg cells are found. Depending on gene expression and functional modules, non-B10 Breg cells exhibited activated TGF-β pathway, thus suggesting that non-B10 Breg cells have specific immunosuppressive properties different from conventional B10 cells. In conclusion, our work provides new insights into Breg cells and illustrates their transcriptional profiles and BCR repertoire in different organs under physiological condition.

关键词： Breg cells scRNA-Seq BCR transcription factor B10 cell

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TGF-β and IL-2 signaling are both required for generating stable thymus regulatory T cells

TGF-β and IL-2 signaling are both required for generating s...

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第十届全国免疫学学术大会

作者： liang Li Yuan Yao Yuqing Xie zhexiong lian Institute of Immunology and School of Life Sciences University of Science and Technology of China

Objective:To investigate the synergic role of TGF-βand IL-2 in regulating the balance between the regulatory T cells and conventional T cells,thus the homeostasis of the immune ***:We crossed dn TGF-βRII mice with C... 详细信息

关键词： TGF-β IL-2 thymus regulatory T cells DNA methylation

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IFN-γ induced LSK(Lin-Sca-1+c-Kit+) cells negatively regulate T cell response in Con A-induced liver injury model

IFN-γ induced LSK(Lin-Sca-1+c-Kit+) cells negatively regula...

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第十届全国免疫学学术大会

作者： Shuhan Yang liang Li Yuan Yao zhexiong lian Institute of Immunology and School of Life Sciences University of Science and Technology of China

Background and Objective:Clinical researches have shown that many diseases such as autoimmune liver disease are often accompanied by hematopoiesis *** our research,we used Con A-induced acute liver injury model to inv... 详细信息

关键词： Con A Liver injury LSK cells IFN-γ

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A Novel Mouse Model of Primary Biliary Cirrhosis by Congenic Bile Duct Protein Immunization

A Novel Mouse Model of Primary Biliary Cirrhosis by Congenic...

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第十届全国免疫学学术大会

作者： Wentao Ma Hongdi Ma Jingbo Yang Qingzhi Liu zhexiong lian Liver Immunology Laboratory Institute of Immunology and The CAS Key Laboratory of Innate Immunity and Chronic Disease School of Life Sciences and Medical Center University of Science and Technology of China

Background/Aim: Primary biliary cirrhosis(PBC) is a typical autoimmune liver disease with a high occurrence in middle-aged women. Histologically, it is characterized by progressive bile duct destruction, with portal lymphocyte infiltration, granulomas, and liver fibrosis. Serologically, 90%-95% PBC patients are positive for anti-mitochondrial antibodies. Clinically, most PBC patients would miss the most proper diagnosis time because of the asymptomatic stage at first. Accordingly, a comprehensive mechanism of PBC is in need urgently. However, patient samples are hard to get, researchers have been dedicated on making an ideal mouse model for easier investigation. Several mouse models are now used to clarify the pathogenesis of PBC but few centered on how the immune tolerance is broken down. Methods: we got a new mouse model of PBC by immunizing female mice with congenic bile duct protein. Results: We found congenic bile duct antigens would efficiently break down the immune tolerance of recipient mice, leading to a phenotype similar with PBC patients. First, our mouse model showed bile duct damage, with inflammation focused of portal tracts. Moreover, flow cytometry analysis demonstrated higher number of CD4+ and CD8+ T cells in the liver and spleen, and these T cells exhibited an activated phenotype. Furthermore, the IFN-γ secreting ability of these T cells was more potent in these immunized mice. Then, we found these mice had greater germinal center reaction ability. At last, we analyzed the anti-mitochondrial antibodies in these mice, and found they are 100% positive for AMA. Conclusion: we defined a novel mouse model of PBC, which would provide help in elucidating the detailed mechanism of this complex disease.

关键词： Bile duct protein Primary biliary cirrhosis Mouse model

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Study of Monosodium Glutamate-induced Mice NAFLD Model

Study of Monosodium Glutamate-induced Mice NAFLD Model

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第十届全国免疫学学术大会

作者： Jingbo Yang Wei Yang Qingzhi Liu Wentao Ma zhexiong lian Liver Immunology Laboratory Institute of Immunology and School of Life Sciences University of Science and Technology of China

Objectives:The prevalence of non-alcoholic fatty liver disease(NAFLD)is increasing worldwide and is often linked with metabolic syndrome and altered immune *** the details of pathogenesis is complicated,yet to be *** a common diet additive,monosodium glutamate(MSG)appear to have toxicity on the neuroendocrine system during infancy stage,and lead to the development of *** want to establish a new NAFLD mouse model based on MSG and figure out the regulatory function of innate immune response in ***:MSG was used during mice infancy stage by hypodermic injection *** addition,high fat diet was added to induce more severe *** Short term of high fat diet and long term of high fat diet were tested in our ***:Compared to control mice,MSG induced greater weight gain,clear hepatosteatosis and mild inflammatory cells *** increasing high fat diet duration,infiltration of immune cells could become much more *** on some innate immune cells,we observed Kupffer cells increased in the liver while PD-L1+Kupffer cells *** also observed decreased NK cells and NKT cells after *** the liver resident DX5-CD49a+NK cells decreased after long term of high fat diet compared to short term high fat *** CXCR3+NK cells were also ***,consistent with up-regulated level of laminins in steatosis liver,the CD29+and CD49a+monocytes were always the most infiltrated cells in our model,independent of the high fat diet ***,we noticed CD29+monocytes have a higher percentage compared to CXCR3+monocytes in total hepatic infiltrated cells,correlated with the pathological features of fatty ***:MSG can be used as an inducer of NAFLD,together with high fat *** MSG-induced alterations in the hepatic innate immune system may contribute to the progress of hepatosteatosis and *** associated signals may be a new aspect for the ther

关键词： MSG NAFLD CD49 CXCR3

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Bioorthognal Equipping CAR-T Cells with Hyaluronidase and Checkpoint Blocking Antibody for Enhanced Solid Tumor Immunotherapy

Bioorthognal Equipping CAR-T Cells with Hyaluronidase and Ch...

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第十四届全国免疫学学术大会

作者： Yangyang Zhao Yansong Dong Shuhan Yang Youyong Yuan zhexiong lian South China University of Technology

Adoptive cellular therapy utilizing Chimeric antigen receptor-redirected T(CAR-T) cells has shown striking therapeutic effects on hematological malignancies. In contrast, the efficacy of treating solid tumors with CAR-T cell therapies is still poor, which is largely due to inefficient penetration into solid tumors and immunosuppressive tumor microenvironment. Herein, we engineered hyaluronidase(HAase) and the checkpoint blocking antibody α-PDL1 on the surface of CAR-T cells via highly efficient and biocompatible bioorthogonal click chemistry to improve the therapeutic effects of CAR-T cells on solid tumors. The modified HAase degrades hyaluronic acid and destroys the tumor extracellular matrix, allowing CAR-T cells penetrate deeply into solid tumors, as evidenced by in vitro infiltration experiments and in vivo biodistribution studies. In addition, in vitro cytotoxicity studies showed stronger antitumor activity of α-PDL1-decorated CAR-T cells than traditional CAR-T cells. Importantly, HAase-and α-PDL1-engineered CAR-T cells showed better therapeutic efficacy on A20 solid tumors, and did not cause significant systemic toxicity. In this work, we provided a simple, efficient, and biologically safe chemical strategy to engineer traditional CAR-T cells for enhanced therapeutic efficacy on solid tumors, which can be extended to other adoptive cellular immunotherapies and holds great potential for clinical application.

关键词： Bioorthogonal reaction Chimeric antigen receptor T cell Immunotherapy Solid tumor

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