Aryl Hydrocarbon Receptor Contributes to the Transcriptional Program of IL-10-Producing Regulatory B Cells

Publication date: 12 November 2019Source: Cell Reports, Volume 29, Issue 7Author(s): Christopher J.M. Piper, Elizabeth C. Rosser, Kristine Oleinika, Kiran Nistala, Thomas Krausgruber, André F. Rendeiro, Aggelos Banos, Ignat Drozdov, Matteo Villa, Scott Thomson, Georgina Xanthou, Christoph Bock, Brigitta Stockinger, Claudia MauriSummaryRegulatory 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.Graphical Abstract
Source: Cell Reports - Category: Cytology Source Type: research