Aryl Hydrocarbon Receptor Contributes to the Transcriptional Program of IL-10-Producing Regulatory B Cells.
Cell Rep
; 29(7): 1878-1892.e7, 2019 11 12.
Article
de En
| MEDLINE
| ID: mdl-31722204
ABSTRACT
Regulatory B cells (Bregs) play a critical role in the control of autoimmunity and inflammation. IL-10 production is the hallmark for the identification of Bregs. However, the molecular determinants that regulate the transcription of IL-10 and control the Breg developmental program remain unknown. Here, we demonstrate that aryl hydrocarbon receptor (AhR) regulates the differentiation and function of IL-10-producing CD19+CD21hiCD24hiBregs and limits their differentiation into B cells that contribute to inflammation. Chromatin profiling and transcriptome analyses show that loss of AhR in B cells reduces expression of IL-10 by skewing the differentiation of CD19+CD21hiCD24hiB cells into a pro-inflammatory program, under Breg-inducing conditions. B cell AhR-deficient mice develop exacerbated arthritis, show significant reductions in IL-10-producing Bregs and regulatory T cells, and show an increase in T helper (Th) 1 and Th17 cells compared with B cell AhR-sufficient mice. Thus, we identify AhR as a relevant contributor to the transcriptional regulation of Breg differentiation.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Transcription génétique
/
Différenciation cellulaire
/
Interleukine-10
/
Récepteurs à hydrocarbure aromatique
/
Facteurs de transcription à motif basique hélice-boucle-hélice
/
Lymphocytes B régulateurs
Type d'étude:
Prognostic_studies
Limites:
Animals
Langue:
En
Journal:
Cell Rep
Année:
2019
Type de document:
Article
Pays d'affiliation:
Royaume-Uni