title: IL-33 promotes innate IFN-γ production and modulates dendritic cell response in LCMV-induced hepatitis in mice.
abstract: Recent studies have revealed IL-33 as a key factor in promoting antiviral T-cell responses. However, it is less clear as to how IL-33 regulates innate immunity. In this study, we infected wild-type (WT) and IL-33(-/-) mice with lymphocytic choriomeningitis virus and demonstrated an essential role of infection-induced IL-33 expression for robust innate IFN-γ production in the liver. We first show that IL-33 deficiency resulted in a marked reduction in the number of IFN-γ(+) γδ T and NK cells, but an increase in that of IL-17(+) γδ T cells at 16 h postinfection. Recombinant IL-33 (rIL-33) treatment could reverse such deficiency via increasing IFN-γ-producing γδ T and NK cells, and inhibiting IL-17(+) γδ T cells. We also found that rIL-33-induced type 2 innate lymphoid cells were not involved in T-cell responses and liver injury, since the adoptive transfer of type 2 innate lymphoid cells neither affected the IFN-γ and TNF-α production in T cells, nor liver transferase levels in lymphocytic choriomeningitis virus infected mice. Interestingly, we found that while IL-33 was not required for costimulatory molecule expression, it was critical for DC proliferation and cytokine production. Together, this study highlights an essential role of IL-33 in regulating innate IFN-γ-production and DC function during viral hepatitis.
authors.affiliation: Department of Microbiology and Immunology, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Yuejin
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, USA.
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, USA.
authors.forename: Lifei
authors.initials: L
authors.lastname: Hou
authors.affiliation: Department of Microbiology and Immunology, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA.|Department of Infectious Diseases, Key Laboratory of Viral Hepatitis of Hunan, Xiangya Hospital, Central South University, Changsha, China.
authors.forename: Panpan
authors.initials: P
authors.lastname: Yi
authors.affiliation: Department of Microbiology and Immunology, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Microbiology and Immunology, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Zakari
authors.initials: Z
authors.lastname: Kwota
authors.affiliation: Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Salvato
authors.affiliation: Department of Immunology, Merck Research Laboratories, Palo Alto, CA, USA.
authors.forename: Rene
authors.initials: R
authors.lastname: de Waal Malefyt
authors.affiliation: Department of Microbiology and Immunology, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA.|Department of Pathology, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA.
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, USA.
authors.forename: Jiaren
authors.initials: J
authors.lastname: Sun
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001117:Arenaviridae Infections / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006505:Hepatitis / Q000276:immunology* / Q000821:virology; D007113:Immunity, Innate / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis*; D000067596:Interleukin-33 / Q000172:deficiency / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: C506535:Il33 protein, mouse; D000067596:Interleukin-33; D007371:Interferon-gamma
keywords: Dendritic cell; IFN-γ; IL-33; Innate lymphoid cell; LCMV; Viral hepatitis; γδ T cell