title: New dog and new tricks: evolving roles for IL-33 in type 2 immunity.
abstract: IL-33 is a more recently identified member of the IL-1 cytokine family, expressed in the nucleus of epithelial cells and released into the extracellular space following tissue damage. The impact of IL-33 as a regulator of the adaptive immune response has been studied extensively, with an understood role for IL-33 in the effector functions of CD4(+) Th2 cells. IL-33, however, is now being shown to initiate the Th2-polarizing function of DCs, and stimulate the secretion of the type 2-associated cytokines, IL-4, IL-5, and IL-13, from tissue-resident innate-immune cells, especially ILCs and MCs. IL-33 also initiates and perpetuates local inflammatory responses through the recruitment and activation of type 2- and inflammatory-associated effectors, such as eosinophils, basophils, and neutrophils. As such, IL-33 drives and amplifies type 2-dependent immunity, as well as type 2-dependent tissue destruction and inflammation. It is also becoming apparent that IL-33 supports the reparative capacity of macrophage and ILCs, but these functions may also contribute to chronic fibrotic diseases. Herein, we review new developments in the understanding of IL-33 as it functions in Th2 cells and type 2 immunity. This includes a discussion of our evolving understanding of how IL-33 directly and indirectly promotes type 2 immune responses through action on innate cells in immunity and the pathogenesis of atopic and fibrotic diseases.
authors: *Starzl Transplantation Institute, Departments of Surgery, Immunology, and Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors: Jeremy M
authors: JM
authors: Lott
authors: *Starzl Transplantation Institute, Departments of Surgery, Immunology, and Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors: Tina L
authors: TL
authors: Sumpter
authors: *Starzl Transplantation Institute, Departments of Surgery, Immunology, and Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA het5@pitt.edu.
authors: Hēth R
authors: HR
authors: Turnquist
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D004847:Epithelial Cells / Q000276:immunology* / Q000473:pathology; D005355:Fibrosis; D005786:Gene Expression Regulation; D006098:Granulocytes / Q000276:immunology / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins / Q000235:genetics / Q000276:immunology*; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000276:immunology; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology; D050791:STAT Transcription Factors / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D018418:Th2 Cells / Q000276:immunology* / Q000473:pathology
chemical_list: C079241:IL1RL1 protein, human; C506536:IL33 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins; D016328:NF-kappa B; D011956:Receptors, Cell Surface; D050791:STAT Transcription Factors; D020928:Mitogen-Activated Protein Kinases
keywords: ST2; T helper cells; fibrosis; immune response; innate-immune cells