The bile acid receptor TGR5 regulates the hematopoietic support capacity of the bone marrow niche

Abstract

The gut is an emerging regulator of bone marrow (BM) hematopoiesis and several signaling molecules are involved in this communication. Among them, bile acids (BAs), originally classified as lipid solubilizers, have emerged as powerful signaling molecules that act as a relay between the digestive system, the microbiota and the rest of the body. The signaling function of BAs relies on specific receptors, including Takeda-G-protein-receptor-5 (TGR5). TGR5 has potent regulatory effects in immune cells, but its effect on the BM as a primary immune organ remains unknown. Here, we investigated the BM of young mice and observed a significant reduction in bone marrow adipose tissue (BMAT) upon loss of TGR5, accompanied by an enrichment in BM adipocyte progenitors which translated into enhanced hematopoietic recovery upon transplantation. These findings open the possibility of modulating stromal hematopoietic support by acting on TGR5 signaling.This work shows that TGR5 loss-of-function reduces regulated bone marrow adipose tissue and accelerates recovery upon bone marrow transplantation. These data highlight TGR5 as key player of the bone marrow microenvironment.