Increased IL-17A secretion in response to Candida albicans in autoimmune polyendocrine syndrome type 1 and its animal model

Ahlgren, KM; Moretti, S; Lundgren, BA; Karlsson, I; Ahlin, E; Norling, A; Hallgren, A; Perheentupa, J; Gustafsson, J; Rorsman, F; Crewther, PE; Ronnelid, J; Bensing, S; Scott, HS; Kampe, O; Romani, L; Lobell, A

Author(s): Ahlgren, KM; Moretti, S; Lundgren, BA; Karlsson, I; Ahlin, E; Norling, A; Hallgren, A; Perheentupa, J; Gustafsson, J; Rorsman, F; Crewther, PE; Ronnelid, J; Bensing, S; Scott, HS; Kampe, O; Romani, L; Lobell, A;
Details: Publication Year 2011-01,Volume 41,Issue #1,Page 235-245
Journal Title: EUROPEAN JOURNAL OF IMMUNOLOGY
Publication Type: Journal Article
Abstract: Autoimmune polyendocrine syndrome type 1 (APS-1) is a multiorgan autoimmune disease caused by mutations in the autoimmune regulator (AIRE) gene. Chronic mucocutaneous candidiasis, hypoparathyroidism and adrenal failure are hallmarks of the disease. The critical mechanisms causing chronic mucocutaneous candidiasis in APS-1 patients have not been identified although autoantibodies to cytokines are implicated in the pathogenesis. To investigate whether the Th reactivity to Candida albicans (C. albicans) and other stimuli was altered, we isolated PBMC from APS-1 patients and matched healthy controls. The Th17 pathway was upregulated in response to C. albicans in APS-1 patients, whereas the IL-22 secretion was reduced. Autoantibodies against IL-22, IL-17A and IL-17F were detected in sera from APS-1 patients by immunoprecipitation. In addition, Aire-deficient (Aire(0/0)) mice were much more susceptible than Aire(+/+) mice to mucosal candidiasis and C. albicans-induced Th17- and Th1-cell responses were increased in Aire(0/0) mice. Thus an excessive IL-17A reactivity towards C. albicans was observed in APS-1 patients and Aire(0/0) mice.
Publisher: WILEY-BLACKWELL PUBLISHING, INC
Keywords: CHRONIC MUCOCUTANEOUS CANDIDIASIS; SYNDROME TYPE-I; GROWTH-FACTOR-BETA; HYPER-IGE SYNDROME; T-CELLS; TH17-ASSOCIATED CYTOKINES; BENEFICIAL AUTOIMMUNITY; TH17 CELLS; DIFFERENTIATION; IMMUNITY
Publisher's Version: https://doi.org/10.1002/eji.200939883
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2011-01-01 12:00:00