PMID- 37265392
OWN - NLM
STAT- MEDLINE
DCOM- 20230718
LR  - 20231213
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 211
IP  - 2
DP  - 2023 Jul 15
TI  - Cutting Edge: Aire Is a Coactivator of the Vitamin D Receptor.
PG  - 175-179
LID - 10.4049/jimmunol.2300207 [doi]
AB  - 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.
CI  - Copyright (c) 2023 by The American Association of Immunologists, Inc.
FAU - Artusa, Patricio
AU  - Artusa P
AD  - Department of Physiology, McGill University, Montreal, Quebec, Canada.
FAU - Lebel, Marie-Eve
AU  - Lebel ME
AD  - Maisonneuve-Rosemont Hospital Research Center, Montreal, Quebec, Canada.
FAU - Barbier, Camille
AU  - Barbier C
AD  - Department of Physiology, McGill University, Montreal, Quebec, Canada.
FAU - Memari, Babak
AU  - Memari B
AUID- ORCID: 0000-0002-4754-6217
AD  - Department of Physiology, McGill University, Montreal, Quebec, Canada.
FAU - Salehi-Tabar, Reyhaneh
AU  - Salehi-Tabar R
AUID- ORCID: 0000-0002-9111-6513
AD  - Department of Physiology, McGill University, Montreal, Quebec, Canada.
FAU - Karabatsos, Sophia
AU  - Karabatsos S
AUID- ORCID: 0009-0004-5695-9728
AD  - Department of Physiology, McGill University, Montreal, Quebec, Canada.
FAU - Ismailova, Aiten
AU  - Ismailova A
AUID- ORCID: 0000-0001-5530-5336
AD  - Department of Physiology, McGill University, Montreal, Quebec, Canada.
FAU - Melichar, Heather J
AU  - Melichar HJ
AUID- ORCID: 0000-0003-0951-334X
AD  - Maisonneuve-Rosemont Hospital Research Center, Montreal, Quebec, Canada.
AD  - Departement de Medecine, Universite de Montreal, Montreal, Quebec, Canada.
FAU - White, John H
AU  - White JH
AUID- ORCID: 0000-0002-4785-2687
AD  - Department of Physiology, McGill University, Montreal, Quebec, Canada.
LA  - eng
GR  - PJT-180271/CIHR/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Receptors, Calcitriol)
RN  - 0 (Transcription Factors)
RN  - 1406-16-2 (Vitamin D)
RN  - 0 (Vdr protein, mouse)
SB  - IM
MH  - Animals
MH  - Mice
MH  - Epithelial Cells
MH  - Gene Expression Regulation
MH  - *Receptors, Calcitriol/metabolism
MH  - Thymus Gland
MH  - *Transcription Factors/genetics/metabolism
MH  - Vitamin D/metabolism
MH  - AIRE Protein
PMC - PMC10315440
COIS- The authors have no financial conflicts of interest.
EDAT- 2023/06/02 13:15
MHDA- 2023/07/05 06:42
PMCR- 2023/06/02
CRDT- 2023/06/02 09:53
PHST- 2023/03/29 00:00 [received]
PHST- 2023/05/08 00:00 [accepted]
PHST- 2023/07/05 06:42 [medline]
PHST- 2023/06/02 13:15 [pubmed]
PHST- 2023/06/02 09:53 [entrez]
PHST- 2023/06/02 00:00 [pmc-release]
AID - 263850 [pii]
AID - jimmunol_2300207 [pii]
AID - 10.4049/jimmunol.2300207 [doi]
PST - ppublish
SO  - J Immunol. 2023 Jul 15;211(2):175-179. doi: 10.4049/jimmunol.2300207.