title: Aire deficient mice develop multiple features of APECED phenotype and show altered immune response.
abstract: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a monogenic autosomal recessive disease caused by mutations in the AIRE gene. Here we have produced knock-out mice for the Aire gene. The Aire-/- mice develop normally; however, autoimmune features of APECED in Aire-/- mice are evident, including multiorgan lymphocytic infiltration, circulating autoantibodies and infertility. The distribution of B and T cells and thymic maturation as well as activation of T cells appear normal, while the TCR-Vbeta repertoire is altered in peripheral T cells of Aire-/- mice. When mice are challenged with immunization, the peripheral T cells of Aire-/- mice have a 3-5-fold increased proliferation. These findings suggest that the Aire gene is not necessary for normal T cell education and development, while a defect in immune response detected in challenged Aire-/- mice underlines the crucial role of AIRE/Aire in maintaining homeostatic regulation in the immune system.
authors.affiliation: Department of Human Genetics, UCLA School of Medicine, Gonda Center, University of California Los Angeles, Los Angeles, CA 90095-7088, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Ramsey
authors.forename: Ola
authors.initials: O
authors.lastname: Winqvist
authors.forename: Lea
authors.initials: L
authors.lastname: Puhakka
authors.forename: Maria
authors.initials: M
authors.lastname: Halonen
authors.forename: Aune
authors.initials: A
authors.lastname: Moro
authors.forename: Olle
authors.initials: O
authors.lastname: Kämpe
authors.forename: Petra
authors.initials: P
authors.lastname: Eskelin
authors.forename: Markku
authors.initials: M
authors.lastname: Pelto-Huikko
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D016516:CD4-CD8 Ratio; D004195:Disease Models, Animal; D018390:Gene Targeting; D007246:Infertility / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D016884:Polyendocrinopathies, Autoimmune / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D000096927:AIRE Protein
chemical_list: D001323:Autoantibodies; D014157:Transcription Factors; D000096927:AIRE Protein