TY - JOUR
T1 - Retinoic acid regulates immune responses by promoting IL-22 and modulating S100 proteins in viral hepatitis
AU - Jie, Zuliang
AU - Liang, Yuejin
AU - Yi, Panpan
AU - Tang, Hui
AU - Soong, Lynn
AU - Cong, Yingzi
AU - Zhang, Kangling
AU - Sun, Jiaren
N1 - Publisher Copyright:
Copyright © 2017 by The American Association of Immunologists, Inc.
PY - 2017/5/1
Y1 - 2017/5/1
N2 - Although large amounts of Vitamin A and its metabolite all-Trans 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.
AB - Although large amounts of Vitamin A and its metabolite all-Trans 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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U2 - 10.4049/jimmunol.1601891
DO - 10.4049/jimmunol.1601891
M3 - Article
C2 - 28363907
AN - SCOPUS:85018478260
SN - 0022-1767
VL - 198
SP - 3448
EP - 3460
JO - Journal of Immunology
JF - Journal of Immunology
IS - 9
ER -