title: IL-33 in T Cell Differentiation, Function, and Immune Homeostasis.
abstract: Recent studies have highlighted a role for the alarmin interleukin (IL)-33 in CD4(+) and CD8(+) T cell activation and function, and have also revealed important distinctions. The IL-33 receptor ST2 is constitutively and abundantly expressed on T-helper-2 (Th2) and GATA-3(+) regulatory T cells in a GATA-3- and STAT5-dependent manner. Upon activation, Th1 and cytotoxic T cells express ST2 transiently, driven by T-bet and/or STAT4. We review these findings here, and critically examine evidence indicating that IL-33 enhances the differentiation and functionality of various T cell subsets through positive feedback loops involving lineage-specifying transcription factors. In this context, we discuss how quantitative and qualitative differences in ST2 expression between effector and GATA-3(+) regulatory T cells may contribute to immune homeostasis, and outline important areas of future inquiry.
authors.affiliation: Experimental Immunology and Osteoarthritis Research, Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany; Pitzer Laboratory of Osteoarthritis Research, German Rheumatism Research Center (DRFZ), Leibniz Institute, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Peine
authors.affiliation: Experimental Immunology and Osteoarthritis Research, Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany; Pitzer Laboratory of Osteoarthritis Research, German Rheumatism Research Center (DRFZ), Leibniz Institute, Charitéplatz 1, 10117 Berlin, Germany; Max Delbrück Center for Molecular Medicine, Robert-Rössle-Str. 10, 13125 Berlin, Germany.
authors.forename: Roman M
authors.initials: RM
authors.lastname: Marek
authors.affiliation: Experimental Immunology and Osteoarthritis Research, Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany; Pitzer Laboratory of Osteoarthritis Research, German Rheumatism Research Center (DRFZ), Leibniz Institute, Charitéplatz 1, 10117 Berlin, Germany. Electronic address: loehning@drfz.de.
authors.forename: Max
authors.initials: M
authors.lastname: Löhning
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D025461:Feedback, Physiological; D050990:GATA3 Transcription Factor / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D006706:Homeostasis; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein / Q000235:genetics / Q000378:metabolism*; D000067596:Interleukin-33 / Q000276:immunology*; D008213:Lymphocyte Activation; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; C079241:IL1RL1 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33
keywords: CD4(+) and CD8(+) T cell subsets; ST2/T1/IL-1RL1; STAT4/STAT5; T-bet/GATA-3/Foxp3; Th1/Th2/Treg/CTL; alarmin IL-33