title: Interleukin-33 promoting Th1 lymphocyte differentiation dependents on IL-12.
abstract: The pro-Th2 cytokine IL-33 is now emerging as an important Th1 cytokine-IFN-γ inducer in murine CD4(+) T cells that is essential for protective cell-mediated immunity against viral infection in mice. However, whether IL-33 can promote human Th1 cell differentiation and how IL-33 polarizes Th1 cells is less understood. We assessed the ability of IL-33 to induce Th1 cell differentiation and IFN-γ production in vitro and in vivo. We report here that IL-33 alone had no ability in Th1 cell polarization. However it potentiated IL-12-mediated Th1 cell differentiation and IFN-γ production in TCR-stimulated murine and human CD4(+) T cells in vitro and in vivo. IL-33 promoted Th1 cell development via MyD88 and synergized with IL-12 to enhance St2 and IL-12R expression in CD4(+) T cells. These data therefore provide a novel mechanism for Th1 cell differentiation and optimal induction of a Type 1 response. Thus, IL-33 is capable of inducing IL-12-dependent Th1 cell differentiation in human and mouse CD4(+) T cells.
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK; Department of Haematology & Immunology, Faculty of Medicine, Umm Al-Qura University, Mecca, KSA, Saudi Arabia.
authors.forename: Mousa
authors.initials: M
authors.lastname: Komai-Koma
authors.affiliation: Department of Pharmacology, Medical Research Council Centre for Drug Safety Science, University of Liverpool, Liverpool, UK.
authors.forename: Eryi
authors.initials: E
authors.lastname: Wang
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
authors.forename: Mariola
authors.initials: M
authors.lastname: Kurowska-Stolarska
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
authors.forename: Charles
authors.initials: C
authors.lastname: McSharry
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK. Electronic address: Damo.Xu@glasgow.ac.uk.
authors.forename: Damo
authors.initials: D
authors.lastname: Xu
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D016207:Cytokines / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000378:metabolism*; D000067596:Interleukin-33 / Q000378:metabolism* / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology* / Q000378:metabolism*
chemical_list: D016207:Cytokines; D000067596:Interleukin-33; D018664:Interleukin-12; D007371:Interferon-gamma
keywords: IFN-γ production; IL-33; Th1 cell development