title: Early IL-17 production by intrahepatic T cells is important for adaptive immune responses in viral hepatitis.
abstract: This study was conducted to examine the interactions among the innate and adaptive immune components of the liver parenchyma during acute viral hepatitis. Mice were i.v. infected with a recombinant adenovirus, and within the first 24 h of infection, we found a transient but significant accumulation of IL-17 and IL-23 in the liver. In vivo neutralization of these interleukins alleviated the liver injury. Further investigations showed that IL-17 neutralization halted the intrahepatic accumulation of CTLs and Th1 cells. A majority of the IL-17-producing cells in the liver were γδ T cells. Additionally, intrahepatic IL-17(+) γδ T cells, but not the IFN-γ(+) ones, preferentially expressed IL-7Rα (CD127) on their surface, which coincided with an elevation of hepatocyte-derived IL-7 at 12 h postinfection. IL-7Rα blockade in vivo severely impeded the expansion of IL-17-producing cells after viral infection. In vitro, IL-7 synergized with IL-23 and directly stimulated IL-17 production from γδ T cells in response to TCRγδ stimulation. Finally, type I IFN (IFN-I) signaling was found to be critical for hepatic IL-7 induction. Collectively, these results showed that the IFN-I/IL-7/IL-17 cascade was important in priming T cell responses in the liver. Moreover, the highly coordinated cross talk among hepatocytes and innate and adaptive immune cells played a critical role in anti-viral immunity in hepatitis.
authors.affiliation: Department of Microbiology and Immunology, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Lifei
authors.initials: L
authors.lastname: Hou
authors.forename: Zuliang
authors.initials: Z
authors.lastname: Jie
authors.forename: Mayura
authors.initials: M
authors.lastname: Desai
authors.forename: Yuejin
authors.initials: Y
authors.lastname: Liang
authors.forename: Lynn
authors.initials: L
authors.lastname: Soong
authors.forename: Tian
authors.initials: T
authors.lastname: Wang
authors.forename: Jiaren
authors.initials: J
authors.lastname: Sun
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D005260:Female; D006524:Hepatitis, Viral, Animal / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D022781:Hepatocytes / Q000276:immunology / Q000378:metabolism; D007370:Interferon Type I / Q000378:metabolism; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000276:immunology; D053759:Interleukin-23 / Q000096:biosynthesis / Q000276:immunology; D015851:Interleukin-7 / Q000378:metabolism; D008099:Liver / Q000276:immunology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*
chemical_list: D007370:Interferon Type I; D020381:Interleukin-17; D053759:Interleukin-23; D015851:Interleukin-7; D016692:Receptors, Antigen, T-Cell, gamma-delta