Retinoic Acid Regulates Immune Responses by Promoting IL-22 and Modulating S100 Proteins in Viral Hepatitis

Overview

Journal J Immunol

Specialty Allergy & Immunology

Date 2017 Apr 2

PMID 28363907

Citations 17

Authors

Zuliang Jie

Yuejin Liang

Panpan Yi

Hui Tang

Lynn Soong

Yingzi Cong

Kangling Zhang

Jiaren Sun

Affiliations

Soon will be listed here.

Abstract

Although large amounts of vitamin A and its metabolite all- retinoic acid (RA) are stored in the liver, how RA regulates liver immune responses during viral infection remains unclear. In this study, we demonstrated that IL-22, mainly produced by hepatic γδ T cells, attenuated liver injury in adenovirus-infected mice. RA can promote γδ T cells to produce mTORC1-dependent IL-22 in the liver, but inhibits IFN-γ and IL-17. RA also affected the aptitude of T cell responses by modulating dendritic cell (DC) migration and costimulatory molecule expression. These results suggested that RA plays an immunomodulatory role in viral infection. Proteomics data revealed that RA downregulated S100 family protein expression in DCs, as well as NF-κB/ERK pathway activation in these cells. Furthermore, adoptive transfer of S100A4-repressed, virus-pulsed DCs into the hind foot of naive mice failed to prime T cell responses in draining lymph nodes. Our study has demonstrated a crucial role for RA in promoting IL-22 production and tempering DC function through downregulating S100 family proteins during viral hepatitis.

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