title: Autoimmunity, Not a Developmental Defect, is the Cause for Subfertility of Autoimmune Regulator (Aire) Deficient Mice.
abstract: Autoimmune regulator's (AIRE) best characterized role is in the generation immunological tolerance, but it is also involved in many other processes such as spermatogenesis. Loss-of-function mutations in AIRE cause a disease called autoimmune polyendocrinopathy, candidiasis and ectodermal dystrophy (APECED; also called autoimmune polyendocrinopathy syndrome type 1, APS-1) that is dominated by various autoimmune manifestations, mainly endocrinopathies. Both patients with APECED and Aire(-/-) mice suffer from varying levels of infertility, but it is not clear if it is a result of an autoimmune tissue damage or more of a developmental defect. In this study, we wanted to resolve whether or not the reduced fertility of Aire(-/-) mice is dependent on the adaptive immune system and therefore a manifestation of autoimmunity in these mice. We generated lymphopenic mice without Aire expression that were devoid of the autoimmune manifestations previously reported in immunocompetent Aire(-/-) mice. These Aire(-/-) Rag1(-/-) mice regained full fertility. This confirms that the development of infertility in Aire(-/-) mice requires a functional adaptive immune system. We also show that only the male Aire(-/-) mice are subfertile, whereas Aire(-/-) females produce litters normally. Moreover, the male subfertility can be adoptively transferred with lymphocytes from Aire(-/-) donor mice to previously fertile lymphopenic Aire(-/-) recipients. Our data show that subfertility in Aire(-/-) mice is dependent on a functional adaptive immune system thus confirming its autoimmune aetiology.
authors.affiliation: Department of Bacteriology and Immunology and Immunobiology Research Program, University of Helsinki, Helsinki, Finland.
authors.forename: E
authors.initials: E
authors.lastname: Kekäläinen
authors.forename: N
authors.initials: N
authors.lastname: Pöntynen
authors.forename: S
authors.initials: S
authors.lastname: Meri
authors.forename: T P
authors.initials: TP
authors.lastname: Arstila
authors.forename: H
authors.initials: H
authors.lastname: Jarva
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics / Q000276:immunology; D019264:Adoptive Transfer; D000818:Animals; D015551:Autoimmunity / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D007246:Infertility / Q000235:genetics*; D017710:Lymphocyte Transfusion; D008214:Lymphocytes / Q000276:immunology; D008231:Lymphopenia / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016884:Polyendocrinopathies, Autoimmune / Q000235:genetics* / Q000276:immunology*; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics*; D000096927:AIRE Protein
chemical_list: D004268:DNA-Binding Proteins; D014157:Transcription Factors; D000096927:AIRE Protein