Cutting Edge: Aire Is a Coactivator of the Vitamin D Receptor

Author:

Artusa Patricio1,Lebel Marie-Ève2,Barbier Camille1,Memari Babak1ORCID,Salehi-Tabar Reyhaneh1ORCID,Karabatsos Sophia1ORCID,Ismailova Aiten1ORCID,Melichar Heather J.23ORCID,White John H.1ORCID

Affiliation:

1. *Department of Physiology, McGill University, Montreal, Quebec, Canada

2. †Maisonneuve-Rosemont Hospital Research Center, Montreal, Quebec, Canada

3. ‡Département de Médecine, Université de Montréal, Montreal, Quebec, Canada

Abstract

Abstract Vitamin D deficiency is associated with the development of autoimmunity, which arises from defects in T cell tolerance to self-antigens. Interactions of developing T cells with medullary thymic epithelial cells, which express tissue-restricted Ags, are essential for the establishment of central tolerance. However, vitamin D signaling in the thymus is poorly characterized. We find that stromal and hematopoietic cells in the mouse thymus express the vitamin D receptor (Vdr) and Cyp27b1, the enzyme that produces hormonal 1,25-dihydroxyvitamin D (1,25D). Treatment of cultured thymic slices with 1,25D enhances expression of the critical medullary thymic epithelial cell transcription factor autoimmune regulator (Aire), its colocalization with the Vdr, and enhances tissue-restricted Ag gene expression. Moreover, the Vdr interacts with Aire in a 1,25D-dependent manner and recruits Aire to DNA at vitamin D response elements, where it acts as a Vdr coactivator. These data link vitamin D signaling directly to critical transcriptional events necessary for central tolerance.

Funder

Canadian HIV Trials Network, Canadian Institutes of Health Research

Publisher

The American Association of Immunologists

Subject

Immunology,Immunology and Allergy

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