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Aryl hydrocarbon receptor contributes to the transcriptional program of IL-10-producing regulatory B cells.

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journal contribution
posted on 22.01.2020 by Christopher JM 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 Mauri
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.

Funding

Crick (Grant ID: 10159, Grant title: Stockinger FC001159)

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