The critical role of myeloid-derived suppressor cells and FXR activation in immune-mediated liver injury

Haiyan Zhang, Yuan Liu, Zhaolian Bian, Shanshan Huang, Xiaofeng Han, Zhengrui You, Qixia Wang, Dekai Qiu, Qi Miao, Yanshen Peng, Xiaoying Li, Pietro Invernizzi, Xiong Ma

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

The immunobiology of FXR has attracted significant attention in immune regulation and innate immunity. We have studied the mechanism of action of FXR activation on two models of acute hepatitis, inflammation mediated by Con A and α-GalCer and focused on the interactions of FXR activation and expression of PIR-B, both invivo and invitro using luciferase reporter and CHIP assays. In addition, based upon our data, we studied the role of FXR activation on the immunobiology of myeloid-derived suppressor cells (MDSCs). Importantly, we report herein that FXR activation reduces the inflammatory insult induced by either α-GalCer or Con A; such treatment expands CD11b<sup>+</sup>Ly6C<sup>+</sup> MDSCs. The protective effect of FXR activation is dependent on expansion of MDSCs, particularly liver CD11b<sup>+</sup>Ly6C<sup>high</sup> cells. Indeed, FXR activation enhances the suppressor function of MDSCs through upregulation of PIR-B by binding the PIR-B promoter. FXR activation drives the accumulation of MDSCs to liver through upregulation of S100A8. FXR activation facilitates homing and function of MDSCs, which function as a critical negative feedback loop in immune-mediated liver injury. The novel mechanisms defined herein emphasize not only the importance of liver lymphoid subpopulations, but also the potential roles of modulating FXR in autoimmune liver disease.

Original languageEnglish (US)
Pages (from-to)55-66
Number of pages12
JournalJournal of Autoimmunity
Volume53
Issue numberC
DOIs
StatePublished - 2014
Externally publishedYes

Keywords

  • Autoimmunity
  • FXR activation
  • Lymphoid subpopulations
  • Myeloid-derived suppressor cells

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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    Zhang, H., Liu, Y., Bian, Z., Huang, S., Han, X., You, Z., Wang, Q., Qiu, D., Miao, Q., Peng, Y., Li, X., Invernizzi, P., & Ma, X. (2014). The critical role of myeloid-derived suppressor cells and FXR activation in immune-mediated liver injury. Journal of Autoimmunity, 53(C), 55-66. https://doi.org/10.1016/j.jaut.2014.02.010