title: IL-33 synergizes with TCR and IL-12 signaling to promote the effector function of CD8+ T cells.
abstract: The effector functions of CD8(+)  T cells are influenced by tissue inflammatory microenvironments. IL-33, a member of the IL-1 family, acts as a danger signal after its release during cell necrosis. The IL-33/ST2 axis has been implicated in various Th2 responses. Its role in CD8(+)  T-cell-mediated immune response is, however, not known. Here we find that type 1 cytotoxic T (Tc1) cells cultured in vitro unexpectedly express high levels of the IL-33 receptor ST2. Interestingly, the expression of ST2 in Tc1 cells is dependent on T-bet, a master Th1/Tc1 transcription factor. In addition, IL-33 enhances TCR-triggered IFN-γ production. IL-33 together with IL-12 can stimulate IFN-γ production in Tc1 cells. Moreover, IL-33 synergizes with IL-12 to promote CD8(+)  T-cell effector function. The synergistic effect of IL-33 and IL-12 is partly mediated by Gadd45b. Together, these in vitro data establish a novel role of IL-33 in promoting effector type 1 adaptive immune responses.
authors: Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
authors: Qianting
authors: Q
authors: Yang
authors: Gang
authors: G
authors: Li
authors: Yibei
authors: Y
authors: Zhu
authors: Lin
authors: L
authors: Liu
authors: Elizabeth
authors: E
authors: Chen
authors: Hēth
authors: H
authors: Turnquist
authors: Xueguang
authors: X
authors: Zhang
authors: Olivera J
authors: OJ
authors: Finn
authors: Xinchun
authors: X
authors: Chen
authors: Binfeng
authors: B
authors: Lu
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002469:Cell Separation; D002478:Cells, Cultured; D005434:Flow Cytometry; D018664:Interleukin-12 / Q000276:immunology* / Q000378:metabolism; D000067596:Interleukin-33; D007378:Interleukins / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D060888:Real-Time Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D000097642:GADD45 Proteins
chemical_list: D000943:Antigens, Differentiation; D018664:Interleukin-12; D000067596:Interleukin-33; D007378:Interleukins; D011948:Receptors, Antigen, T-Cell; C490125:Gadd45b protein, mouse; D000097642:GADD45 Proteins; C506535:Il33 protein, mouse