title: IL-33 induces skin inflammation with mast cell and neutrophil activation.
abstract: Psoriasis is a common chronic autoimmune condition of the skin characterized by hyperplasia of epidermal keratinocytes associated with pro-inflammatory cytokines. IL-33 is a new member of the IL-1 superfamily that signals through the ST2 receptor and was originally defined as an inducer of T helper 2 (Th2) cytokines. Recently, broader immune activatory potential has been defined for IL-33 particularly via mast cell activation and neutrophil migration. Here, we show that ST2(-/-) mice exhibit reduced cutaneous inflammatory responses compared with WT mice in a phorbol ester-induced model of skin inflammation. Furthermore, injections of IL-33 into the ears of mice induce an inflammatory skin lesion. This inflammatory response was partially dependent on mast cells as mast cell-deficient mice (Kit(W-sh/W-sh) ) showed delayed responses to IL-33. IL-33 also recruited neutrophils to the ear, an effect mediated in part by increased production of the chemokine KC (CXCL1). Finally, we show that IL-33 expression is up-regulated in the epidermis of clinical psoriatic lesions, compared with healthy skin. These results therefore demonstrate that IL-33 may play a role in psoriasis-like plaque inflammation. IL-33 targeting may provide a new treatment strategy for psoriasis.
authors.affiliation: Glasgow Biomedical Research Centre, University of Glasgow, UK. axel.hueber@uk-erlangen.de
authors.forename: Axel J
authors.initials: AJ
authors.lastname: Hueber
authors.forename: Jose C
authors.initials: JC
authors.lastname: Alves-Filho
authors.forename: Darren L
authors.initials: DL
authors.lastname: Asquith
authors.forename: Chesney
authors.initials: C
authors.lastname: Michels
authors.forename: Neal L
authors.initials: NL
authors.lastname: Millar
authors.forename: James H
authors.initials: JH
authors.lastname: Reilly
authors.forename: Gerry J
authors.initials: GJ
authors.lastname: Graham
authors.forename: Foo Y
authors.initials: FY
authors.lastname: Liew
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Miller
authors.forename: Iain B
authors.initials: IB
authors.lastname: McInnes
mesh_terms: D000818:Animals; D054360:Chemokine CXCL1 / Q000276:immunology / Q000378:metabolism; D003872:Dermatitis / Q000209:etiology / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins / Q000276:immunology* / Q000378:metabolism / Q000633:toxicity; D008297:Male; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018375:Neutrophil Activation / Q000276:immunology; D020556:Neutrophil Infiltration / Q000276:immunology; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D011565:Psoriasis / Q000276:immunology / Q000378:metabolism; D018123:Receptors, Interleukin / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity
chemical_list: D054360:Chemokine CXCL1; C475895:Cxcl1 protein, mouse; C506536:IL33 protein, human; C486189:Il1rl1 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins; D018123:Receptors, Interleukin; D013755:Tetradecanoylphorbol Acetate