E-MTAB-7345 - RNASeq: Aryl hydrocarbon receptor governs a transcriptional programme that determines regulatory B cell differentiation and function
Last updated on 15 October 2019, released on 15 October 2019
Regulatory B cells (Breg) play a critical role in the control of autoimmunity and inflammation. Although IL-10 is considered the hallmark for the identification of Bregs, the molecular programme that controls IL-10 production in Bregs is yet to be defined. Here, we demonstrate that aryl hydrocarbon receptor (AhR) controls the differentiation and function of IL-10-producing Bregs. Deficiency of AhR-expressing B cells drastically reduces IL-10 production by B cells. This leads to the unrestrained differentiation of T helper (Th)17 cells and a significant reduction in the percentage of regulatory T cells (Treg), which increases the severity of experimental arthritis when compared to control animals with AhR-sufficient B cells. A combination of chromatin-landscape profiling by ATAC-seq and transcriptome analyses by RNA-seq demonstrated that a loss of AhR expression in B cells not only reduces IL-10 expression by Bregs, defined as CD21hiCD24hi B cells, but also promotes a pro-inflammatory programme in CD21hiCD24hi B cells, even under Breg inducing conditions. Thus, AhR acts as a master transcriptional regulator of Breg differentiation by implementing a molecular programme that controls IL-10 production and represses pro-inflammatory cytokine production.
RNA-seq of coding RNA, compound treatment design, genetic modification design