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

Cell Rep. 2019 Nov 12;29(7):1878-1892.e7. doi: 10.1016/j.celrep.2019.10.018.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / immunology
  • B-Lymphocytes, Regulatory / cytology
  • B-Lymphocytes, Regulatory / immunology*
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / immunology*
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology*
  • Interleukin-10 / genetics
  • Interleukin-10 / immunology*
  • Mice
  • Mice, Knockout
  • Receptors, Aryl Hydrocarbon / genetics
  • Receptors, Aryl Hydrocarbon / immunology*
  • Th1 Cells / cytology
  • Th1 Cells / immunology
  • Th17 Cells / cytology
  • Th17 Cells / immunology
  • Transcription, Genetic / immunology*


  • Ahr protein, mouse
  • Antigens, CD
  • Basic Helix-Loop-Helix Transcription Factors
  • IL10 protein, mouse
  • Receptors, Aryl Hydrocarbon
  • Interleukin-10