Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Piper, CJM; Rosser, EC; Oleinika, K; Nistala, K; Krausgruber, T; Rendeiro, APF; Banos, A; Drozdov, I; Villa, M; Thomson, S; Xanthou, G; Bock, C; Stockinger, B; Mauri, C.
Aryl Hydrocarbon Receptor Contributes to the Transcriptional Program of IL-10-Producing Regulatory B Cells
CELL REP. 2019; 29(7): 1878-+.
Doi: 10.1016/j.celrep.2019.10.018
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- Co-authors Med Uni Graz
- Villa Matteo
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- 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 programremain unknown. Here, wedemonstrate that aryl hydrocarbon receptor (AhR) regulates the differentiation and function of IL-10-producing CD19(+)CD21(hi)CD24(hi)Bregs 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(+)CD21(hi)CD24(hi)B cells into a pro-inflammatory program, under Breg-inducing conditions. B cell AhR-deficient mice developexacerbated arthritis, showsignificant 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.