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

Date

2011

Authors

Ahlgren, K.
Moretti, S.
Lundgren, B.
Karlsson, I.
Ahlin, E.
Norling, A.
Hallgren, A.
Perheentupa, J.
Gustafsson, J.
Rorsman, F.

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Journal article

Citation

European Journal of Immunology, 2011; 41(1):235-245

Statement of Responsibility

Kerstin M. Ahlgren, Silvia Moretti, Brita Ardesjö Lundgren, Iulia Karlsson, Erik Åhlin, Anna Norling, Åsa Hallgren, Jaakko Perheentupa, Jan Gustafsson, Fredrik Rorsman, Pauline E. Crewther, Johan Rönnelid, Sophie Bensing, Hamish S. Scott, Olle Kämpe, Luigina Romani and Anna Lobell

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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.

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Data source: Supporting information, https://doi.org/10.1002/eji.200939883 Link to a related website: https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/eji.200939883, Open Access via Unpaywall

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Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

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