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In this study, we demonstrated that IL-22, mainly produced by hepatic \u03b3\u03b4 T cells, attenuated liver injury in adenovirus-infected mice. RA can promote \u03b3\u03b4 T cells to produce mTORC1-dependent IL-22 in the liver, but inhibits IFN-\u03b3 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-\u03baB\/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.<\/jats:p>","DOI":"10.4049\/jimmunol.1601891","type":"journal-article","created":{"date-parts":[[2017,4,1]],"date-time":"2017-04-01T00:40:32Z","timestamp":1491007232000},"page":"3448-3460","source":"Crossref","is-referenced-by-count":29,"title":["Retinoic Acid Regulates Immune Responses by Promoting IL-22 and Modulating S100 Proteins in Viral Hepatitis"],"prefix":"10.1093","volume":"198","author":[{"given":"Zuliang","family":"Jie","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Institute for Human Infections and Immunity, University of Texas Medical Branch , Galveston, TX 77555-1070"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9557-1847","authenticated-orcid":false,"given":"Yuejin","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Institute for Human Infections and Immunity, University of Texas Medical Branch , Galveston, TX 77555-1070"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panpan","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Institute for Human Infections and Immunity, University of Texas Medical Branch , Galveston, TX 77555-1070"},{"name":"Department of Infectious Diseases, Key Laboratory of Viral Hepatitis of Hunan, Xiangya Hospital, Central South University , Changsha 410008,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Institute for Human Infections and Immunity, University of Texas Medical Branch , Galveston, TX 77555-1070"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynn","family":"Soong","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Institute for Human Infections and Immunity, University of Texas Medical Branch , Galveston, TX 77555-1070"},{"name":"Department of Pathology, Institute for Human Infections and Immunity, University of Texas Medical Branch , Galveston, TX 77555-1070"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4167-7395","authenticated-orcid":false,"given":"Yingzi","family":"Cong","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Institute for Human Infections and Immunity, University of Texas Medical Branch , Galveston, TX 77555-1070"},{"name":"Department of Pathology, Institute for Human Infections and Immunity, University of Texas Medical Branch , Galveston, TX 77555-1070"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kangling","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Institute for Human Infections and Immunity, University of Texas Medical Branch , Galveston, TX 77555-1070"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5084-4437","authenticated-orcid":false,"given":"Jiaren","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Institute for Human Infections and Immunity, University of Texas Medical Branch , Galveston, TX 77555-1070"},{"name":"Department of Pathology, Institute for Human Infections and Immunity, University of Texas Medical Branch , Galveston, TX 77555-1070"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,5,1]]},"reference":[{"key":"2025030615104471600_r1","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1111\/j.1478-3231.2010.02262.x","article-title":"Acute liver failure: mechanisms of immune-mediated liver injury","volume":"30","author":"Wu","year":"2010","journal-title":"Liver Int."},{"key":"2025030615104471600_r2","doi-asserted-by":"crossref","first-page":"621","DOI":"10.4049\/jimmunol.1201970","article-title":"Early IL-17 production by intrahepatic T cells is important for adaptive immune responses in viral hepatitis","volume":"190","author":"Hou","year":"2013","journal-title":"J. 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