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.
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.
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DOI：
10.1016/j.biocel.2014.07.005
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发表时间：
2014-09
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通讯作者：
Kai Zhu;N. Zhang;Nining Guo;Juhao Yang;Jianrong Wang;Chunhui Yang;Chunfu Yang;Lian Zhu;Chunliang Xu;Q. Deng;Ruihong Zhu;Honglin Wang;Xuejin Chen;Yufang Shi;Yao Li;Q. Leng
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作者：
Kai Zhu;N. Zhang;Nining Guo;Juhao Yang;Jianrong Wang;Chunhui Yang;Chunfu Yang;Lian Zhu;Chunliang Xu;Q. Deng;Ruihong Zhu;Honglin Wang;Xuejin Chen;Yufang Shi;Yao Li;Q. Leng
骨髓源性抑制细胞（MDSC）在维持肿瘤和炎性疾病的免疫耐受中发挥重要作用。已经在人类和小鼠模型的肝炎中描述了几种肝脏MDSC。尽管所有的鼠MDSC都是CD 11b +Gr-1+，但它们的真实表型和抑制机制仍然难以捉摸。这项研究表明，SSC高CD 11b高Ly-6C高Ly-6 G低单核细胞，而不是其他肝脏浸润，CD 11b +Gr-1+亚群可以抑制CD 4 T细胞反应。当与CD 4 T细胞共培养时，它们的抑制活性即使在1：50的比例下也是显著有效的。从机制上讲，这种抑制依赖于诱导型一氧化氮合酶（iNOS）产生的一氧化氮。此外，发现这些肝脏MDSC的抑制功能需要与活化的CD 4 T细胞直接接触。连续转移实验表明，这些肝脏MDSCs可以显着改善伴刀豆球蛋白A（Con A）诱导的小鼠暴发性肝炎。最后，MDSC介导的体内抑制依赖于iNOS的表达。总之，SSC高CD 11bhighLy-6ChhighLy-6 Glowcells代表了炎症肝脏中真正的MDSC，并可能起到最小化肝炎感染后过度CD 4 T细胞反应引起的附带损伤的作用。
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 SSChighCD11bhighLy-6ChighLy-6Glowmonocytic 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 suppressionin vivowas dependent on iNOS expression. Altogether, SSChighCD11bhighLy-6ChighLy-6Glowcells 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.