IL-33 induces skin inflammation with mast cell and neutrophil activation

Hueber, A. J., Alves-Filho, J. C., Asquith, D. L., Michels, C., Millar, N. L. , Reilly, J. H., Graham, G. J. , Liew, F. Y., Miller, A. M. and McInnes, I. B. (2011) IL-33 induces skin inflammation with mast cell and neutrophil activation. European Journal of Immunology, 41(8), pp. 2229-2237. (doi:10.1002/eji.201041360) (PMID:21674479)

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Publisher's URL: http://dx.doi.org/10.1002/eji.201041360

Abstract

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 exhibited reduced cutaneous inflammatory responses compared to WT mice in a phorbol ester-induced model of skin inflammation. Furthermore, injections of IL-33 into the ears of mice induced an inflammatory skin lesion. This inflammatory response was partially dependent on mast cells as mast cell deficient mice (Kit<sup>W-sh/W-sh</sup>) 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 to 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

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McInnes, Professor Iain and Liew, Professor Foo and Michels, Dr Chesney and Reilly, Mr James and Asquith, Dr Darren and Miller, Dr Ashley and Hueber, Dr Axel and Millar, Dr Neal and Alves-Filho, Dr Jose and Graham, Professor Gerard
Authors: Hueber, A. J., Alves-Filho, J. C., Asquith, D. L., Michels, C., Millar, N. L., Reilly, J. H., Graham, G. J., Liew, F. Y., Miller, A. M., and McInnes, I. B.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:European Journal of Immunology
Publisher:Wiley-VCH Verlag
ISSN:0014-2980
ISSN (Online):1521-4141
Published Online:24 June 2011

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
514422Regulation of the adaptive immune response by chemokine scavenging receptorsGerard GrahamMedical Research Council (MRC)G0901113Infection Immunity and Inflammation Medicine
486461The role of IL-35 in infection and inflammationFoo LiewMedical Research Council (MRC)G0801198III -IMMUNOLOGY
483611Interleukin-33: A Novel Cytokine in the Inflammation of Atherosclerosis and ObesityAshley MillerBritish Heart Foundation (BHF)FS/08/035/25309III -IMMUNOLOGY
483612Interleukin-33: A Novel Cytokine in the Inflammation of Atherosclerosis and ObesityAshley MillerBritish Heart Foundation (BHF)FS/08/035/25309III -IMMUNOLOGY