title: AIRE deficiency leads to impaired iNKT cell development.
abstract: Autoimmune Polyendocrine Syndrome type I (APS I) is caused by mutations in the Autoimmune Regulator gene (AIRE), and results in the immunological destruction of endocrine organs. Herein we have characterized the CD1d-restricted invariant NKT cells (iNKT) and NK cells in APS I patients and Aire(-/-) mice, two cell populations known to play a role in the regulation of autoimmune disease. We show that the frequency of circulating iNKT cells is reduced in APS I patients compared to healthy controls. In accordance with this, iNKT cells are significantly reduced in the thymus and peripheral organs of Aire(-/-) mice. Bone marrow transfer from wild type donors into lethally irradiated Aire(-/-) recipients led to a decreased iNKT cell population in the liver, suggesting an impaired development of iNKT cells in the absence of Aire expression in radio-resistant cells. In contrast to the iNKT cells, both conventional NK cells and thymus-derived NK cells were unaffected by Aire deficiency and differentiated normally in Aire(-/-) mice. Our results show that expression of Aire in radio-resistant cells is important for the development of iNKT cells, whereas NK cell development and function does not depend on Aire.
authors: Karolinska Institutet, Department of Medicine, Clinical Allergy Research Unit, Stockholm, Sweden.
authors: Emma
authors: E
authors: Lindh
authors: Eleftheria
authors: E
authors: Rosmaraki
authors: Louise
authors: L
authors: Berg
authors: Hanna
authors: H
authors: Brauner
authors: Mikael C I
authors: MC
authors: Karlsson
authors: Leena
authors: L
authors: Peltonen
authors: Petter
authors: P
authors: Höglund
authors: Ola
authors: O
authors: Winqvist
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D055611:Natural Killer T-Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016884:Polyendocrinopathies, Autoimmune / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011828:Radiation Chimera; D011836:Radiation Tolerance / Q000235:genetics; D013950:Thymus Gland / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000096927:AIRE Protein
chemical_list: D014157:Transcription Factors; D000096927:AIRE Protein