Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
IL-25: A Cytokine Linking Eosinophils and Adaptative Immunity in Churg-Strauss Syndrome.
Terrier1, Benjamin, Bieche2, Ivan, Maisonobe1, Thierry, Laurendeau2, Ingrid, Rosenzwajg1, Michele, Diemert1, Marie-Claude, Musset1, Lucile
Churg-Strauss Syndrome (CSS) is characterized by systemic vasculitis, and blood and tissue eosinophilia. Blood eosinophils correlate with disease activity. Activated T cells from CSS patients are predominantly Th2. IL-25 has been shown to license innate and adaptive immunity by enhancing Th2 cytokines production.
To analyze whether eosinophils could elicit a Th2 mediated immune response in CSS, we sought to determine the implication of IL-25 and its receptor IL-17RB in the pathogenesis of CSS.
We performed quantitative measurement of serum human IL-25 by ELISA, analysis of cell surface markers and cytokine production by flow cytometry and Luminex. Immunohistochemical analysis and gene quantification with mRNA on peripheral nerve biopsy samples of active CSS patients, patients with microscopic polyangiitis (MPA; disease controls) and controls with non-inflammatory axonopathy.
We found increased level of IL-25 in the serum of active patient with CSS (952±697 vs. 75±49 pg/ml in inactive patients and 47±6 pg/ml in healthy donors). IL-25 correlated with disease activity and eosinophils blood level. Eosinophils were the main source of IL-25, whereas activated CD4 memory T cells were the main IL-17RB (IL-25 receptor) expressing cells in CSS. IL-25 enhanced the production of IL-4, IL-5 and IL-13 by activated peripheral blood monocytes. IL-25 and IL-17RB were observed within the vasculitic lesions of patients with CSS, and IL-17RB co-localized with T cells. Increased expression of IL-17RB, TRAF6 and JunB in vasculitic lesions of CSS underscored the IL-25-mediated activation, whereas up-regulation of GATA3 and IL-10 supported Th2 differentiation.
Our study is the first to demonstrate the implication of IL-25 in the pathogenesis of CSS and its correlation with disease activity. Eosinophils, through the production of IL-25, may exert a critical role in promoting Th2 responses in peripheral blood and target tissues in CSS, and represent a potential target for novel therapy.
To cite this abstract, please use the following information:
Terrier, Benjamin, Bieche, Ivan, Maisonobe, Thierry, Laurendeau, Ingrid, Rosenzwajg, Michele, Diemert, Marie-Claude, et al; IL-25: A Cytokine Linking Eosinophils and Adaptative Immunity in Churg-Strauss Syndrome. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :2025