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

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.

• Authors: Kerstin M Ahlgren, Silvia Moretti, Brita Ardesjö Lundgren, Iulia Karlsson, Erik Ahlin, Anna Norling, Asa Hallgren, Jaakko Perheentupa, Jan Gustafsson, Fredrik Rorsman, Pauline E Crewther, Johan Rönnelid, Sophie Bensing, Hamish S Scott, Olle Kämpe, Luigina Romani, Anna Lobell
• Journal: European journal of immunology (Eur J Immunol) Vol. 41 Issue 1 Pg. 235-45 (Jan 2011) ISSN: 1521-4141 [Electronic] Germany
• PMID: 21182094 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• APECED protein
• Autoantibodies
• IL17A protein, human
• Il17a protein, mouse
• Interleukin-17
• Interleukins
• Transcription Factors
• interleukin-22

Topics

• Adolescent
• Adult
• Animals
• Autoantibodies (blood, immunology)
• Candida albicans (immunology)
• Candidiasis (immunology)
• Disease Models, Animal
• Female
• Humans
• Interleukin-17 (immunology)
• Interleukins (immunology, metabolism)
• Leukocytes, Mononuclear (immunology)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Mutant Strains
• Middle Aged
• Polyendocrinopathies, Autoimmune (immunology)
• Th17 Cells (immunology)
• Transcription Factors (genetics)
• Up-Regulation (immunology)
• Young Adult