SSChighCD11bhighLy-6ChighLy-6G low myeloid cells curtail CD4 T cell response by inducible nitric oxide synthase in murine hepatitis

Kai Zhu, Na Zhang, Nining Guo, Juhao Yang, Jianrong Wang, Chunhui Yang, Chunfu Yang, Lian Zhu, Chunliang Xu, Qiang Deng, Ruihong Zhu, Honglin Wang, Xuejin Chen, Yufang Shi, Yao Li, Qibin Leng

Research output: Contribution to journalArticle

11 Scopus citations

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 SSChighCD11bhighLy-6ChighLy-6Glow 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, SSChighCD11b highLy-6ChighLy-6Glow 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.

Original languageEnglish (US)
Pages (from-to)89-97
Number of pages9
JournalInternational Journal of Biochemistry and Cell Biology
Volume54
DOIs
Publication statusPublished - Sep 2014
Externally publishedYes

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Keywords

  • CD4 T cell response
  • Concanavalin A
  • Hepatitis
  • MDSC
  • Nitric oxide

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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