Aryl hydrocarbon receptor activity downstream of IL-10 signaling is required to promote regulatory functions in human dendritic cells.

ABSTRACT: Interleukin (IL)-10 is a main player in peripheral immune tolerance, the physiological mechanism preventing immune reactions to self/harmless antigens. Here, we investigate IL-10-induced molecular mechanisms generating tolerogenic dendritic cells (tolDC) from monocytes. Using genomic studies, we show that IL-10 induces a pattern of accessible enhancers exploited by aryl hydrocarbon receptor (AHR) to promote expression of a set of core genes. We demonstrate that AHR activity occurs downstream of IL-10 signaling in myeloid cells and is required for the induction of tolerogenic activities in DC. Analyses of circulating DCs show that IL-10/AHR genomic signature is active in vivo in health. In multiple sclerosis patients, we instead observe significantly altered signature correlating with funct

SUBMITTER: Avancini D 

PROVIDER: S-EPMC10066577 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature