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    Glucagon-like peptide-1 (GLP-1) and the regulation of human invariant natural killer Tcells: lessons from obesity, diabetes and psoriasis


    Hogan, A.E. and Tobin, A.M. and Ahern, T. and Corrigan, M.A. and Gaoatswe, G. and Jackson, R. and O’Reilly, V. and Lynch, L. and Doherty, D.G. and Moynagh, Paul N. and Kirby, B. and O’Connell, J. and O'Shea, D. (2011) Glucagon-like peptide-1 (GLP-1) and the regulation of human invariant natural killer Tcells: lessons from obesity, diabetes and psoriasis. Diabetologia, 54 (11). pp. 2745-2754. ISSN 0012-186X

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    Abstract

    Aims/hypothesis The innate immune cells, invariant natural killer T cells (iNKT cells), are implicated in the pathogenesis of psoriasis, an inflammatory condition associated with obesity and other metabolic diseases, such as diabetes and dyslipidaemia. We observed an improvement in psoriasis severity in a patient within days of starting treatment with an incretin-mimetic, glucagon-like peptide-1 (GLP-1) receptor agonist. This was independent of change in glycaemic control. We proposed that this unexpected clinical outcome resulted from a direct effect of GLP-1 on iNKTcells. Methods We measured circulating and psoriatic plaque iNKT cell numbers in two patients with type 2 diabetes and psoriasis before and after commencing GLP-1 analogue therapy. In addition, we investigated the in vitro effects of GLP-1 on iNKT cells and looked for a functional GLP-1 receptor on these cells. Results The Psoriasis Area and Severity Index improved in both patients following 6 weeks of GLP-1 analogue therapy. This was associated with an alteration in iNKT cell number, with an increased number in the circulation and a decreased number in psoriatic plaques. The GLP-1 receptor was expressed on iNKT cells, and GLP-1 induced a dose-dependent inhibition of iNKT cell cytokine secretion, but not cytolytic degranulation in vitro. Conclusions/interpretation The clinical effect observed and the direct interaction between GLP-1 and the immune system raise the possibility of therapeutic applications for GLP-1 in inflammatory conditions such as psoriasis.

    Item Type: Article
    Additional Information: The definitive version of this article is available at DOI 10.1007/s00125-011-2232-3
    Keywords: Anti-inflammatory; CREB; Diabetes; GLP-1 analogue; GLP-1 receptor; Innate immune system; Invariant NKT cells; Obesity; Psoriasis; Institute of Immunology; National University of Ireland Maynooth;
    Academic Unit: Faculty of Science and Engineering > Biology
    Faculty of Science and Engineering > Research Institutes > Institute of Immunology
    Item ID: 4281
    Depositing User: Professor Paul Moynagh
    Date Deposited: 27 Mar 2013 17:15
    Journal or Publication Title: Diabetologia
    Publisher: Springer Verlag
    Refereed: Yes
    URI:

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