title: Interleukin-33 in Tissue Homeostasis, Injury, and Inflammation.
abstract: Interleukin-33 (IL-33) is a nuclear-associated cytokine of the IL-1 family originally described as a potent inducer of allergic type 2 immunity. IL-33 signals via the receptor ST2, which is highly expressed on group 2 innate lymphoid cells (ILC2s) and T helper 2 (Th2) cells, thus underpinning its association with helminth infection and allergic pathology. Recent studies have revealed ST2 expression on subsets of regulatory T cells, and for a role for IL-33 in tissue homeostasis and repair that suggests previously unrecognized interactions within these cellular networks. IL-33 can participate in pathologic fibrotic reactions, or, in the setting of microbial invasion, can cooperate with inflammatory cytokines to promote responses by cytotoxic NK cells, Th1 cells, and CD8(+) T cells. Here, we highlight the regulation and function of IL-33 and ST2 and review their roles in homeostasis, damage, and inflammation, suggesting a conceptual framework for future studies.
authors.affiliation: Department of Microbiology & Immunology, University of California, San Francisco, 94143-0795, USA; Department of Laboratory Medicine, University of California, San Francisco, 94143-0795, USA.
authors.forename: Ari B
authors.initials: AB
authors.lastname: Molofsky
authors.affiliation: Howard Hughes Medical Institute, University of California, San Francisco, 94143-0795, USA; Department of Microbiology & Immunology, University of California, San Francisco, 94143-0795, USA.
authors.forename: Adam K
authors.initials: AK
authors.lastname: Savage
authors.affiliation: Howard Hughes Medical Institute, University of California, San Francisco, 94143-0795, USA; Department of Medicine, University of California, San Francisco, 94143-0795, USA; Department of Microbiology & Immunology, University of California, San Francisco, 94143-0795, USA. Electronic address: locksley@medicine.ucsf.edu.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Locksley
mesh_terms: D000818:Animals; D003602:Cytotoxicity, Immunologic; D006706:Homeostasis / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology*; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins / Q000276:immunology / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014947:Wounds and Injuries / Q000276:immunology*
chemical_list: C079241:IL1RL1 protein, human; C506536:IL33 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins; D011956:Receptors, Cell Surface