Interleukin-25: a cytokine linking eosinophils and adaptive immunity in Churg-Strauss syndrome

Churg-Strauss syndrome (CSS) is characterized by systemic vasculitis and blood and tissue eosinophilia. Blood eosinophilia correlates with disease activity, and activated T cells from CSS patients are predominantly T helper 2 (Th2). Interleukin (IL)-25 has been shown to link innate and adaptive immu...

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Veröffentlicht in:Blood 2010-11, Vol.116 (22), p.4523-4531
Hauptverfasser: Terrier, Benjamin, Bièche, Ivan, Maisonobe, Thierry, Laurendeau, Ingrid, Rosenzwajg, Michèlle, Kahn, Jean-Emmanuel, Diemert, Marie-Claude, Musset, Lucile, Vidaud, Michel, Sène, Damien, Costedoat-Chalumeau, Nathalie, Le Thi-Huong, Du, Amoura, Zahir, Klatzmann, David, Cacoub, Patrice, Saadoun, David
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Sprache:eng
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Zusammenfassung:Churg-Strauss syndrome (CSS) is characterized by systemic vasculitis and blood and tissue eosinophilia. Blood eosinophilia correlates with disease activity, and activated T cells from CSS patients are predominantly T helper 2 (Th2). Interleukin (IL)-25 has been shown to link innate and adaptive immunity by enhancing Th2 cytokine production. We sought to determine the involvement of IL-25 and its receptor IL-17RB in the pathogenesis of CSS. We found increased levels of IL-25 in the serum of active CSS patients (952 ± 697 vs 75 ± 49 pg/mL in inactive patients and 47 ± 6 pg/mL in healthy donors). IL-25 was correlated with disease activity and eosinophil level. Eosinophils were the main source of IL-25, whereas activated CD4+ memory T cells were the IL-17RB–expressing cells in CSS. IL-25 enhanced the production of IL-4, IL-5, and IL-13 by activated peripheral blood mononuclear cells. IL-25 and IL-17RB were observed within the vasculitic lesions of patients with CSS, and IL-17RB colocalized with T cells. Increased expression of IL-17RB, tumor necrosis factor receptor–associated factor 6, 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 findings suggest that eosinophils, through the production of IL-25, exert a critical role in promoting Th2 responses in target tissues of CSS.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2010-02-267542