title: Intrahepatic innate lymphoid cells secrete IL-17A and IL-17F that are crucial for T cell priming in viral infection.
abstract: Intrahepatic cell-derived, early IL-17 is important for activating APCs in viral infection; however, the source and regulation of this IL-17 surge in the liver microenvironment are not well defined. In this article, we present evidence for a significant expansion of IL-17A/F-producing cells in mouse liver within 24 h of adenovirus infection. In addition to γδ T cells, a subset of IL-17A/F(+) cells expressed no myeloid or lymphoid lineage markers. Instead, they expressed high levels of stem cell markers, IL-7R and RORγt, consistent with the newly described innate lymphoid cells (ILCs). Based on their unique surface markers and cytokine profiles, these cells were confirmed as group 3 ILCs. In addition to adenovirus infection, group 3 ILCs were also found in mouse liver within 24 h of lymphocytic choriomeningitis virus infection. They contributed significantly to the establishment of the early cytokine milieu in virus-infected liver. Functional studies with mice deficient of IL-17R, IL-17A, and IL-17F further revealed that IL-17 signaling was critical for priming T cell responses in viral hepatitis. IL-17A repressed IL-17F secretion in vitro and in vivo; IL-17F(+) intrahepatic cells expanded more vigorously in IL-17A knockout animals, permitting efficient Ag presentation and T cell function. However, IL-17F neither inhibited IL-17A in vitro nor regulated its secretion in vivo. Together, this study has demonstrated the importance of a unique intrahepatic subpopulation and subsequent IL-17A/F regulation at initial stages of viral infection in the liver. These results have important implications for anticytokine biologic therapy and vaccine development.
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555;
authors.forename: Zuliang
authors.initials: Z
authors.lastname: Jie
authors.forename: Yuejin
authors.initials: Y
authors.lastname: Liang
authors.forename: Lifei
authors.initials: L
authors.lastname: Hou
authors.forename: Chen
authors.initials: C
authors.lastname: Dong
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Lynn
authors.initials: L
authors.lastname: Soong
authors.forename: Yingzi
authors.initials: Y
authors.lastname: Cong
authors.forename: Jiaren
authors.initials: J
authors.lastname: Sun
mesh_terms: D000256:Adenoviridae / Q000276:immunology / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D054370:Chemokine CXCL9 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D054884:Host-Pathogen Interactions / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000821:virology; D008214:Lymphocytes / Q000145:classification / Q000276:immunology* / Q000378:metabolism; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology / Q000378:metabolism; D053722:Receptors, Interleukin-17 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014777:Virus Diseases / Q000276:immunology* / Q000821:virology
chemical_list: D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; C491673:Il17ra protein, mouse; D020381:Interleukin-17; D016692:Receptors, Antigen, T-Cell, gamma-delta; D053722:Receptors, Interleukin-17; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma