| First Author | Yu M | Year | 2021 |
| Journal | J Clin Invest | Volume | 131 |
| Issue | 4 | PubMed ID | 33586672 |
| Mgi Jnum | J:336539 | Mgi Id | MGI:7486337 |
| Doi | 10.1172/JCI143137 | Citation | Yu M, et al. (2021) Ovariectomy induces bone loss via microbial-dependent trafficking of intestinal TNF+ T cells and Th17 cells. J Clin Invest 131(4) |
| abstractText | Estrogen deficiency causes a gut microbiome-dependent expansion of BM Th17 cells and TNF-alpha-producing T cells. The resulting increased BM levels of IL-17a (IL-17) and TNF stimulate RANKL expression and activity, causing bone loss. However, the origin of BM Th17 cells and TNF+ T cells is unknown. Here, we show that ovariectomy (ovx) expanded intestinal Th17 cells and TNF+ T cells, increased their S1P receptor 1-mediated (S1PR1-mediated) egress from the intestine, and enhanced their subsequent influx into the BM through CXCR3- and CCL20-mediated mechanisms. Demonstrating the functional relevance of T cell trafficking, blockade of Th17 cell and TNF+ T cell egress from the gut or their influx into the BM prevented ovx-induced bone loss. Therefore, intestinal T cells are a proximal target of sex steroid deficiency relevant for bone loss. Blockade of intestinal T cell migration may represent a therapeutic strategy for the treatment of postmenopausal bone loss. |
