title: Retinoic Acid Regulates Immune Responses by Promoting IL-22 and Modulating S100 Proteins in Viral Hepatitis.
abstract: Although large amounts of vitamin A and its metabolite all-transretinoic 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.
authors.affiliation: Department of Microbiology and Immunology, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555-1070.
authors.forename: Zuliang
authors.initials: Z
authors.lastname: Jie
authors.affiliation: Department of Microbiology and Immunology, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555-1070.
authors.forename: Yuejin
authors.identifier: 0000-0002-9557-1847
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Microbiology and Immunology, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555-1070.|Department of Infectious Diseases, Key Laboratory of Viral Hepatitis of Hunan, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Panpan
authors.initials: P
authors.lastname: Yi
authors.affiliation: Department of Pharmacology and Toxicology, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555-1070; and.
authors.forename: Hui
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of Microbiology and Immunology, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555-1070.|Department of Pathology, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555-1070.
authors.forename: Lynn
authors.initials: L
authors.lastname: Soong
authors.affiliation: Department of Microbiology and Immunology, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555-1070.|Department of Pathology, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555-1070.
authors.forename: Yingzi
authors.identifier: 0000-0003-4167-7395
authors.initials: Y
authors.lastname: Cong
authors.affiliation: Department of Pharmacology and Toxicology, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555-1070; and.
authors.forename: Kangling
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Microbiology and Immunology, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555-1070; jisun@utmb.edu.|Department of Pathology, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555-1070.
authors.forename: Jiaren
authors.identifier: 0000-0001-5084-4437
authors.initials: J
authors.lastname: Sun
mesh_terms: D000256:Adenoviridae / Q000276:immunology*; D000818:Animals; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D005260:Female; D006524:Hepatitis, Viral, Animal / Q000188:drug therapy*; D007111:Immunity, Cellular / Q000187:drug effects / Q000235:genetics; D007155:Immunologic Factors / Q000627:therapeutic use*; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D000071999:S100 Calcium-Binding Protein A4 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology; D014212:Tretinoin / Q000627:therapeutic use*; D000097043:Interleukin-22
chemical_list: D007155:Immunologic Factors; D007378:Interleukins; D016328:NF-kappa B; D000071999:S100 Calcium-Binding Protein A4; D014212:Tretinoin; D000097043:Interleukin-22; C470944:S100a4 protein, mouse