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

Yuejin Liang, Zuliang Jie, Panpan Yi, Xianxiu Wan, Wei Wang, Hui Tang, Zakari Kwota, Lynn Soong, Yingzi Cong, Kangling Zhang and Jiaren Sun
J Immunol May 1, 2016, 196 (1 Supplement) 196.13;
Yuejin Liang
1Univ. of Texas Med. Br., Galveston
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Zuliang Jie
1Univ. of Texas Med. Br., Galveston
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Panpan Yi
1Univ. of Texas Med. Br., Galveston
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Xianxiu Wan
1Univ. of Texas Med. Br., Galveston
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Wei Wang
1Univ. of Texas Med. Br., Galveston
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Hui Tang
1Univ. of Texas Med. Br., Galveston
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Zakari Kwota
1Univ. of Texas Med. Br., Galveston
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Lynn Soong
1Univ. of Texas Med. Br., Galveston
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Yingzi Cong
1Univ. of Texas Med. Br., Galveston
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Kangling Zhang
1Univ. of Texas Med. Br., Galveston
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Jiaren Sun
1Univ. of Texas Med. Br., Galveston
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Abstract

The effector T cell responses promote viral clearance and disease resolution in viral hepatitis, but can also mediate tissue damage; however, much less is known as to how the liver protects itself against the injury. In this study, we have revealed a retinoic acid (RA)-mediated, hepatoprotective mechanism in adenovirus-induced hepatitis in mice. We found that RA treatment promoted hepatoprotective cytokine IL-22, but inhibited the pro-inflammatory factor IL-17, from gd T and double-negative T cells, and that the hepatic IL-17 and IL-22 production were regulated via the mTOR/PI3K signaling pathway. Moreover, we found that RA modulated the magnitude of antigen-specific T cell responses via down-regulating dendritic cell (DC) co-stimulatory molecule expression and its migratory capacity. Mechanistically, RA treatment inhibited Calcium-binding S100 family proteins (S100A4/6/10) and the NF-κB/ERK signaling pathways on DCs. The inhibition of novel S100A4 resulted in impaired DC migration from inflamed tissues to lymph nodes for T cell priming. Collectively, our study has revealed a previously unappreciated role and molecular mechanism of RA in modulating immune responses and protecting the liver from viral hepatitis.

  • Copyright © 2016 by The American Association of Immunologists, Inc.
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The Journal of Immunology
Vol. 196, Issue 1 Supplement
1 May 2016
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Retinoic acid regulates immune responses by promoting IL-22 production and modulating S100 protein in viral hepatitis
Yuejin Liang, Zuliang Jie, Panpan Yi, Xianxiu Wan, Wei Wang, Hui Tang, Zakari Kwota, Lynn Soong, Yingzi Cong, Kangling Zhang, Jiaren Sun
The Journal of Immunology May 1, 2016, 196 (1 Supplement) 196.13;

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Retinoic acid regulates immune responses by promoting IL-22 production and modulating S100 protein in viral hepatitis
Yuejin Liang, Zuliang Jie, Panpan Yi, Xianxiu Wan, Wei Wang, Hui Tang, Zakari Kwota, Lynn Soong, Yingzi Cong, Kangling Zhang, Jiaren Sun
The Journal of Immunology May 1, 2016, 196 (1 Supplement) 196.13;
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  • PI3K/mTOR-dependent IL-22 production modulates polyfunctional T cell responses in viral hepatitis.
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Print ISSN 0022-1767        Online ISSN 1550-6606