論文 - 詳細
| 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* |
| IF | 11.864 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 8 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC05738 |