Retinoic acid regulates immune responses by promoting IL-22 and modulating S100 proteins in viral hepatitis

Zuliang Jie, Yuejin Liang, Panpan Yi, Hui Tang, Lynn Soong, Yingzi Cong, Kangling Zhang, Jiaren Sun

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)3448-3460
Number of pages13
JournalJournal of Immunology
Volume198
Issue number9
DOIs
StatePublished - May 1 2017

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S100 Proteins
Tretinoin
Hepatitis
T-Lymphocytes
Liver
Virus Diseases
Dendritic Cells
Down-Regulation
Interleukin-17
Adoptive Transfer
MAP Kinase Signaling System
interleukin-22
Vitamin A
Adenoviridae
Proteomics
Cell Movement
Foot
Hepatocytes
Lymph Nodes
Viruses

ASJC Scopus subject areas

  • Immunology

Cite this

Retinoic acid regulates immune responses by promoting IL-22 and modulating S100 proteins in viral hepatitis. / Jie, Zuliang; Liang, Yuejin; Yi, Panpan; Tang, Hui; Soong, Lynn; Cong, Yingzi; Zhang, Kangling; Sun, Jiaren.

In: Journal of Immunology, Vol. 198, No. 9, 01.05.2017, p. 3448-3460.

Research output: Contribution to journalArticle

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AU - Soong, Lynn

AU - Cong, Yingzi

AU - Zhang, Kangling

AU - Sun, Jiaren

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