| RRC ID |
87001
|
| 著者 |
Yu M, Pal S, Paterson CW, Li JY, Tyagi AM, Adams J, Coopersmith CM, Weitzmann MN, Pacifici R.
|
| タイトル |
Ovariectomy induces bone loss via microbial-dependent trafficking of intestinal TNF+ T cells and Th17 cells.
|
| ジャーナル |
J Clin Invest
|
| Abstract |
Estrogen deficiency causes a gut microbiome-dependent expansion of BM Th17 cells and TNF-α-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.
|
| 巻・号 |
131(4)
|
| 公開日 |
2021-2-15
|
| DOI |
10.1172/JCI143137
|
| PII |
143137
|
| PMID |
33586672
|
| PMC |
PMC7880410
|
| MeSH |
Animals
Cell Movement / immunology*
Chemokine CCL20 / genetics
Chemokine CCL20 / immunology
Female
Humans
Intestines* / immunology
Intestines* / microbiology
Mice
Mice, Knockout
Osteoporosis, Postmenopausal* / immunology
Osteoporosis, Postmenopausal* / microbiology
Ovariectomy*
Receptors, CXCR3 / genetics
Receptors, CXCR3 / immunology
Th17 Cells / immunology*
Tumor Necrosis Factor-alpha / genetics
Tumor Necrosis Factor-alpha / immunology*
|
| リソース情報 |
| 実験動物マウス |
RBRC05738 |
