title: Critical roles of conventional dendritic cells in promoting T cell-dependent hepatitis through regulating natural killer T cells.
abstract: Dendritic cells (DCs) play critical roles in initiating and regulating innate immunity as well as adaptive immune responses. However, the role of conventional dendritic cells (cDCs) in concanavalin A (ConA)-induced fulminant hepatitis is unknown. In this study, we demonstrated that depletion of cDCs using either CD11c-diphtheria toxin receptor transgenic mice (DTR Tg) mice or anti-CD11c antibody reduced the severity of liver injury significantly, indicating a detrimental role of cDCs in ConA-induced hepatitis. We elucidated further the pathological role of cDCs as being the critical source of interleukin (IL)-12, which induced the secretion of interferon (IFN)-γ by natural killer (NK) T cells. Reconstitution of cDCs-depleted mice with IL-12 restored ConA-induced hepatitis significantly. Furthermore, we determined that NK T cells were the target of DC-derived IL-12, and NK T cells contributed to liver inflammation and injury through production of IFN-γ. In summary, our study demonstrated a novel function of cDCs in mediating ConA-induced hepatitis through regulating IFN-γ secretion of NK T cells in an IL-12-dependent fashion. Targeting cDCs might provide potentially therapeutic applications in treating autoimmune related liver diseases.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: X
authors.initials: X
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: J
authors.initials: J
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: H
authors.initials: H
authors.lastname: Zhao
authors.affiliation: The First Affiliate Hospital, Biomedical Translational Research Institute, Guangdong Province Key Laboratory of Molecular Immunology and Antibody Engineering, Jinan University, Guangzhou, China.
authors.forename: J
authors.initials: J
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Li
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: X
authors.initials: X
authors.lastname: Qi
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Collaborative Innovation Center for Biotherapy, Sichuan University, Chengdu, Sichuan, China.
authors.forename: L
authors.initials: L
authors.lastname: Bai
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: L
authors.initials: L
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Hong
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China.|Department of Immunology, St Jude Children's Research Hospital, Memphis, TN, USA.|University of Science and Technology of China, Hefei City, Anhui, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Yin
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015415:Biomarkers; D002450:Cell Communication / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D006505:Hepatitis / Q000276:immunology* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D056747:Immunomodulation; D016130:Immunophenotyping; D018836:Inflammation Mediators / Q000378:metabolism; D017114:Liver Failure, Acute / Q000209:etiology / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008111:Liver Function Tests; D051379:Mice; D008822:Mice, Transgenic; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators
keywords: IFN-γ; IL-12; cDCs; hepatitis