title: IL-17C/IL-17RE Augments T Cell Function in Autoimmune Hepatitis.
abstract: Autoimmune hepatitis is a worldwide health problem and significant cause of mortality. However, the disease etiology is largely unknown, which accounts for ineffective treatment and uncontrolled disease progression. In this study, we demonstrated the functional importance of the IL-17C/IL-17RE axis in Con A-induced hepatitis. Elevated IL-17C expression was detected in liver samples of both human and mouse autoimmune hepatitis. IL-17C, produced by hepatocytes, and its specific receptor IL-17RE on liver-resident T cells were both found to be required in Con A-induced liver damage. Mechanistically, IL-17C augmented the expression of IL-2 by intrahepatic CD4+ T cells to promote NK cell activation and liver damage. To our knowledge, our findings thus for the first time defined the indispensable role of IL-17C/IL-17RE in autoimmune hepatitis; this axis may serve as a novel drug target for the treatment of this disease.
authors.affiliation: Institute for Immunology, Tsinghua University, Beijing 100084, China.|School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Jinling
authors.initials: J
authors.lastname: Huang
authors.affiliation: Organ Transplantation Center, Organ Transplantation Institute, 309th Hospital, Beijing 100091, China.
authors.forename: Qing
authors.identifier: 0000-0001-5402-5316
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: Shanghai Public Health Clinical Center, Shanghai 201058, China; and.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Immunology and Pathogen Biology, Tongji University School of Medicine, Shanghai 200092, China.
authors.forename: Lan
authors.identifier: 0000-0001-8732-1998
authors.initials: L
authors.lastname: Yin
authors.affiliation: Institute for Immunology, Tsinghua University, Beijing 100084, China.|School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Shanjuan
authors.initials: S
authors.lastname: Hong
authors.affiliation: Institute for Immunology, Tsinghua University, Beijing 100084, China.|School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Zhongjun
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Institute for Immunology, Tsinghua University, Beijing 100084, China; chendong@tsinghua.edu.cn wjin@tsinghua.edu.cn.|School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jin
authors.affiliation: Institute for Immunology, Tsinghua University, Beijing 100084, China; chendong@tsinghua.edu.cn wjin@tsinghua.edu.cn.|School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Chen
authors.identifier: 0000-0002-2673-4200
authors.initials: C
authors.lastname: Dong
mesh_terms: D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D019693:Hepatitis, Autoimmune / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D020381:Interleukin-17 / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction; D053722:Receptors, Interleukin-17 / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D020381:Interleukin-17; D053722:Receptors, Interleukin-17