title: 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.affiliation: Department of Medical Sciences, Uppsala University, Uppsala, Sweden. Kerstin.Ahlgren@medsci.uu.se
authors.forename: Kerstin M
authors.initials: KM
authors.lastname: Ahlgren
authors.forename: Silvia
authors.initials: S
authors.lastname: Moretti
authors.forename: Brita Ardesjö
authors.initials: BA
authors.lastname: Lundgren
authors.forename: Iulia
authors.initials: I
authors.lastname: Karlsson
authors.forename: Erik
authors.initials: E
authors.lastname: Ahlin
authors.forename: Anna
authors.initials: A
authors.lastname: Norling
authors.forename: Asa
authors.initials: A
authors.lastname: Hallgren
authors.forename: Jaakko
authors.initials: J
authors.lastname: Perheentupa
authors.forename: Jan
authors.initials: J
authors.lastname: Gustafsson
authors.forename: Fredrik
authors.initials: F
authors.lastname: Rorsman
authors.forename: Pauline E
authors.initials: PE
authors.lastname: Crewther
authors.forename: Johan
authors.initials: J
authors.lastname: Rönnelid
authors.forename: Sophie
authors.initials: S
authors.lastname: Bensing
authors.forename: Hamish S
authors.initials: HS
authors.lastname: Scott
authors.forename: Olle
authors.initials: O
authors.lastname: Kämpe
authors.forename: Luigina
authors.initials: L
authors.lastname: Romani
authors.forename: Anna
authors.initials: A
authors.lastname: Lobell
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D002176:Candida albicans / Q000276:immunology*; D002177:Candidiasis / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology*; D007378:Interleukins / Q000276:immunology / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D008875:Middle Aged; D016884:Polyendocrinopathies, Autoimmune / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics; D015854:Up-Regulation / Q000276:immunology; D055815:Young Adult; D000096927:AIRE Protein; D000097043:Interleukin-22
chemical_list: D001323:Autoantibodies; D020381:Interleukin-17; D007378:Interleukins; D014157:Transcription Factors; D000096927:AIRE Protein; D000097043:Interleukin-22; C508717:IL17A protein, human; C098680:Il17a protein, mouse