title: SSC(high)CD11b(high)Ly-6C(high)Ly-6G(low) myeloid cells curtail CD4 T cell response by inducible nitric oxide synthase in murine hepatitis.
abstract: Myeloid-derived suppressor cells (MDSCs) play an important role in maintaining immune tolerance in response to tumors and inflammatory diseases. Several liver MDSCs have been described in hepatitis in humans and mouse models. Although all the murine MDSCs are CD11b(+)Gr-1(+), their true phenotype and mechanism of suppression remain elusive. This study revealed that SSC(high)CD11b(high)Ly-6C(high)Ly-6G(low) monocytic cells but not the other liver-infiltrating, CD11b(+)Gr-1(+) subsets could suppress CD4 T cell responses. Their suppressive activity was remarkably effective even at a ratio of 1:50 when co-cultured with CD4 T cells. Mechanistically, the suppression was dependent on nitric oxide production by inducible nitric oxide synthase (iNOS). Furthermore, the suppressive function by these liver MDSCs was found to require direct contact with activated CD4 T cells. Adoptive transfer experiments demonstrate that these liver MDSCs can dramatically ameliorate concanavalin A (Con A)-induced fulminant hepatitis in mice. Finally, MDSC-mediated suppression in vivo was dependent on iNOS expression. Altogether, SSC(high)CD11b(high)Ly-6C(high)Ly-6G(low) cells represent authentic MDSCs in the inflammatory liver and may function to minimize collateral damage caused by an overzealous CD4 T cell response following hepatitis infection.
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Nining
authors.initials: N
authors.lastname: Guo
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Juhao
authors.initials: J
authors.lastname: Yang
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Jianrong
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Chunhui
authors.initials: C
authors.lastname: Yang
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Chunfu
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Laboratory Animal Sciences, Shanghai Jiaotong University School of Medicine, 280 South Chongqing Road, Shanghai 200025, China.
authors.forename: Lian
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Chunliang
authors.initials: C
authors.lastname: Xu
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Deng
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Ruihong
authors.initials: R
authors.lastname: Zhu
authors.affiliation: Shanghai Institute of Immunology, Shanghai Jiaotong University School of Medicine, 280 South Chongqing Road, Shanghai 200025, China.
authors.forename: Honglin
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Laboratory Animal Sciences, Shanghai Jiaotong University School of Medicine, 280 South Chongqing Road, Shanghai 200025, China.
authors.forename: Xuejin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.
authors.forename: Yufang
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Laboratory Animal Sciences, Shanghai Jiaotong University School of Medicine, 280 South Chongqing Road, Shanghai 200025, China. Electronic address: yao.li.shsmu@gmail.com.
authors.forename: Yao
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China. Electronic address: qbleng@sibs.ac.cn.
authors.forename: Qibin
authors.initials: Q
authors.lastname: Leng
mesh_terms: D000123:Acetyltransferases / Q000378:metabolism*; D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism*; D039481:CD11b Antigen / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D000081031:Fatty Acid Elongases; D005260:Female; D005434:Flow Cytometry; D006505:Hepatitis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D007108:Immune Tolerance; D007165:Immunosuppression Therapy; D017114:Liver Failure, Acute / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000502:physiology*
chemical_list: D000950:Antigens, Ly; D039481:CD11b Antigen; C494192:Ly-6C antigen, mouse; C480309:Ly6G antigen, mouse; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D000123:Acetyltransferases; D000081031:Fatty Acid Elongases
keywords: CD4 T cell response; Concanavalin A; Hepatitis; MDSC; Nitric oxide