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 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.
Terrier
Benjamin
B
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.
Bièche
Ivan
I
Maisonobe
Thierry
T
Laurendeau
Ingrid
I
Rosenzwajg
Michèlle
M
Kahn
Jean-Emmanuel
JE
Diemert
Marie-Claude
MC
Musset
Lucile
L
Vidaud
Michel
M
Sène
Damien
D
Costedoat-Chalumeau
Nathalie
N
Le Thi-Huong
Du
D
Amoura
Zahir
Z
Klatzmann
David
D
Cacoub
Patrice
P
Saadoun
David
D
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
C408922:IL17RB protein, human; D020381:Interleukin-17; D018123:Receptors, Interleukin; D053722:Receptors, Interleukin-17