title: Interleukin-25: a cytokine linking eosinophils and adaptive immunity in Churg-Strauss syndrome.
abstract: 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.
authors: Laboratory I3, Immunology, Immunopathology, Immunotherapy, Unité Mixte de Recherche 7211, Centre National de la Recherche Scientifique/Université Pierre et Marie Curie, Institut National de la Santé et de la Recherche Médicale U959, France.
authors: Benjamin
authors: B
authors: Terrier
authors: Ivan
authors: I
authors: Bièche
authors: Thierry
authors: T
authors: Maisonobe
authors: Ingrid
authors: I
authors: Laurendeau
authors: Michèlle
authors: M
authors: Rosenzwajg
authors: Jean-Emmanuel
authors: JE
authors: Kahn
authors: Marie-Claude
authors: MC
authors: Diemert
authors: Lucile
authors: L
authors: Musset
authors: Michel
authors: M
authors: Vidaud
authors: Damien
authors: D
authors: Sène
authors: Nathalie
authors: N
authors: Costedoat-Chalumeau
authors: Du
authors: D
authors: Le Thi-Huong
authors: Zahir
authors: Z
authors: Amoura
authors: David
authors: D
authors: Klatzmann
authors: Patrice
authors: P
authors: Cacoub
authors: David
authors: D
authors: Saadoun
mesh_terms: D056704:Adaptive Immunity; D000293:Adolescent; D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D015267:Churg-Strauss Syndrome / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D004804:Eosinophils / Q000276:immunology*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D020381:Interleukin-17 / Q000097:blood / Q000235:genetics / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D018123:Receptors, Interleukin / Q000235:genetics / Q000276:immunology; D053722:Receptors, Interleukin-17; D014657:Vasculitis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D055815:Young Adult
chemical_list: C408922:IL17RB protein, human; D020381:Interleukin-17; D018123:Receptors, Interleukin; D053722:Receptors, Interleukin-17