title: Targeting IL-33 in autoimmunity and inflammation.
abstract: Interleukin-33 (IL-33) belongs to the IL-1 family of cytokines. Whereas IL-1 is processed and released by live immune cells in response to infection or other triggers, IL-33 is mostly released as a danger signal ("alarmin") from damaged cells. IL-33 may also be processed and released from activated mast cells (MCs) with subsequent autocrine and paracrine actions. IL-33 augments the stimulatory effects of IgE and substance P on MCs but can also trigger release of cytokines from MCs on its own. Blood IL-33 levels are increased in asthma, atopic dermatitis, multiple sclerosis, rheumatoid arthritis, and Sjögren's syndrome. However, prolonged elevation of IL-33 downregulates FcεRI and may be protective in atherosclerosis, suggesting different roles in immune-regulated diseases. Even though neutralizing IL-33, knocking-down its receptor, or using its soluble "decoy" receptor has resulted in anti-inflammatory effects, there appear to be different outcomes in different tissues. Hence, selective regulation of IL-33 synthesis, release, and signaling may be required to provide effective treatment options.
authors.affiliation: Laboratory of Molecular Immunopharmacology and Drug Discovery, Department of Integrative Physiology and Pathobiology (T.C.T., A.I.P., A.T., S.P.), Graduate Program in Pharmacology and Experimental Therapeutics, Sackler School of Graduate Biomedical Sciences (T.C.T., A.T.), Department of Internal Medicine (T.C.T.), Tufts University School of Medicine, and Tufts Medical Center (T.C.T.), Boston, Massachusetts; and Immunology Division, Graduate Medical School, University of Chieti-Pescara, Chieti, Italy (P.C.) theoharis.theoharides@tufts.edu.
authors.forename: Theoharis C
authors.initials: TC
authors.lastname: Theoharides
authors.affiliation: Laboratory of Molecular Immunopharmacology and Drug Discovery, Department of Integrative Physiology and Pathobiology (T.C.T., A.I.P., A.T., S.P.), Graduate Program in Pharmacology and Experimental Therapeutics, Sackler School of Graduate Biomedical Sciences (T.C.T., A.T.), Department of Internal Medicine (T.C.T.), Tufts University School of Medicine, and Tufts Medical Center (T.C.T.), Boston, Massachusetts; and Immunology Division, Graduate Medical School, University of Chieti-Pescara, Chieti, Italy (P.C.).
authors.forename: Anastasia I
authors.initials: AI
authors.lastname: Petra
authors.affiliation: Laboratory of Molecular Immunopharmacology and Drug Discovery, Department of Integrative Physiology and Pathobiology (T.C.T., A.I.P., A.T., S.P.), Graduate Program in Pharmacology and Experimental Therapeutics, Sackler School of Graduate Biomedical Sciences (T.C.T., A.T.), Department of Internal Medicine (T.C.T.), Tufts University School of Medicine, and Tufts Medical Center (T.C.T.), Boston, Massachusetts; and Immunology Division, Graduate Medical School, University of Chieti-Pescara, Chieti, Italy (P.C.).
authors.forename: Alexandra
authors.initials: A
authors.lastname: Taracanova
authors.affiliation: Laboratory of Molecular Immunopharmacology and Drug Discovery, Department of Integrative Physiology and Pathobiology (T.C.T., A.I.P., A.T., S.P.), Graduate Program in Pharmacology and Experimental Therapeutics, Sackler School of Graduate Biomedical Sciences (T.C.T., A.T.), Department of Internal Medicine (T.C.T.), Tufts University School of Medicine, and Tufts Medical Center (T.C.T.), Boston, Massachusetts; and Immunology Division, Graduate Medical School, University of Chieti-Pescara, Chieti, Italy (P.C.).
authors.forename: Smaro
authors.initials: S
authors.lastname: Panagiotidou
authors.affiliation: Laboratory of Molecular Immunopharmacology and Drug Discovery, Department of Integrative Physiology and Pathobiology (T.C.T., A.I.P., A.T., S.P.), Graduate Program in Pharmacology and Experimental Therapeutics, Sackler School of Graduate Biomedical Sciences (T.C.T., A.T.), Department of Internal Medicine (T.C.T.), Tufts University School of Medicine, and Tufts Medical Center (T.C.T.), Boston, Massachusetts; and Immunology Division, Graduate Medical School, University of Chieti-Pescara, Chieti, Italy (P.C.).
authors.forename: Pio
authors.initials: P
authors.lastname: Conti
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000378:metabolism*; D000067596:Interleukin-33; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism; D018123:Receptors, Interleukin / Q000378:metabolism
chemical_list: C506536:IL33 protein, human; D000067596:Interleukin-33; D007378:Interleukins; D018123:Receptors, Interleukin