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Apoptotic cells induce immunosuppression through dendritic cells: Critical roles of IFN-gamma and nitric oxide
Ren GW1; Su JJ2; Zhao X1; Zhang LY1; Zhang JM1; Roberts AI1; Zhang HT2; Das G1; Shi YF*1,2; shiyu@umdnj.edu
2008
发表期刊JOURNAL OF IMMUNOLOGY
ISSN0022-1767
卷号181期号:5页码:3277-3284
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摘要Apoptotic cells induce immunosuppression through unknown mechanisms. To identify the underlying molecular mediators, we examined how apoptotic cells induce immunoregulation by dendritic cells (DC). We found that administration of DC exposed to apoptotic cells (DCap) strongly inhibited the expansion of lymphocytes in draining lymph nodes in vivo and the subsequent Ag-specific activation of these lymphocytes ex vivo. Unexpectedly, Map supported T cell activation to a similar extent as normal DC in vitro, leading to proliferation and IL-2 production, except that DCap did not support T cell production of IFN-gamma. Surprisingly, when DCap were cocultured with normal DC, they completely lost their ability to support T cell activation, an effect reversed by anti-IFN-gamma or inhibitors of inducible NO synthase (iNOS). As expected, exposure to apoptotic cells rendered DC.,, capable of producing much more NO in response to exogenous IFN-gamma than normal DC. Furthermore, DCap from iNOS(-/-) or IFN-gamma RI-/- mice were not inhibitory in vitro or in vivo. Therefore, the IFN-gamma-induced production of NO by apoptotic cell-sensitized DC plays a key role in apoptotic cell-mediated immunosuppression.
资助者This work was supported in part by New Jersey Commission on Science and Technology (NJCST-2042-014-84), United States Public Health Service Grants (AI057596 and AI50222), and the National Space Biomedical Research Institute (IIH00405), which is supported ; This work was supported in part by New Jersey Commission on Science and Technology (NJCST-2042-014-84), United States Public Health Service Grants (AI057596 and AI50222), and the National Space Biomedical Research Institute (IIH00405), which is supported ; This work was supported in part by New Jersey Commission on Science and Technology (NJCST-2042-014-84), United States Public Health Service Grants (AI057596 and AI50222), and the National Space Biomedical Research Institute (IIH00405), which is supported ; This work was supported in part by New Jersey Commission on Science and Technology (NJCST-2042-014-84), United States Public Health Service Grants (AI057596 and AI50222), and the National Space Biomedical Research Institute (IIH00405), which is supported
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收录类别SCI
语种英语
资助者This work was supported in part by New Jersey Commission on Science and Technology (NJCST-2042-014-84), United States Public Health Service Grants (AI057596 and AI50222), and the National Space Biomedical Research Institute (IIH00405), which is supported ; This work was supported in part by New Jersey Commission on Science and Technology (NJCST-2042-014-84), United States Public Health Service Grants (AI057596 and AI50222), and the National Space Biomedical Research Institute (IIH00405), which is supported ; This work was supported in part by New Jersey Commission on Science and Technology (NJCST-2042-014-84), United States Public Health Service Grants (AI057596 and AI50222), and the National Space Biomedical Research Institute (IIH00405), which is supported ; This work was supported in part by New Jersey Commission on Science and Technology (NJCST-2042-014-84), United States Public Health Service Grants (AI057596 and AI50222), and the National Space Biomedical Research Institute (IIH00405), which is supported
文献类型期刊论文
条目标识符http://ir.kiz.ac.cn/handle/152453/4431
专题分子免疫生物学
通讯作者shiyu@umdnj.edu
作者单位1.Department of Molecular Genetics, Microbiology and Immunology, Robert Wood John- son Medical School-University of Medicine and Dentistry of New Jersey, Piscataway, NJ 08854
2.School of Life Science, University of Science and Technology of China and Overseas Immunobiology Team, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, People’s Republic of China
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Ren GW,Su JJ,Zhao X,et al. Apoptotic cells induce immunosuppression through dendritic cells: Critical roles of IFN-gamma and nitric oxide[J]. JOURNAL OF IMMUNOLOGY,2008,181(5):3277-3284.
APA Ren GW.,Su JJ.,Zhao X.,Zhang LY.,Zhang JM.,...&shiyu@umdnj.edu.(2008).Apoptotic cells induce immunosuppression through dendritic cells: Critical roles of IFN-gamma and nitric oxide.JOURNAL OF IMMUNOLOGY,181(5),3277-3284.
MLA Ren GW,et al."Apoptotic cells induce immunosuppression through dendritic cells: Critical roles of IFN-gamma and nitric oxide".JOURNAL OF IMMUNOLOGY 181.5(2008):3277-3284.
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