{"doi":"10.1172/jci143137","title":"Ovariectomy induces bone loss via microbial-dependent trafficking of intestinal TNF+ T cells and Th17 cells","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.","journal":"Journal of Clinical Investigation","year":2021,"id":147737,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":147,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9541,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":251680,"name":"Subhashis Pal","orcid":"0000-0002-3916-5545","position":1,"is_corresponding":false},{"id":536859,"name":"Cameron W. Paterson","orcid":"0000-0003-1541-2537","position":2,"is_corresponding":false},{"id":253201,"name":"Jau‐Yi Li","orcid":null,"position":3,"is_corresponding":false},{"id":251681,"name":"Abdul Malik Tyagi","orcid":"0000-0001-9012-5779","position":4,"is_corresponding":false},{"id":57872,"name":"Jon Adams","orcid":"0000-0002-9901-5717","position":5,"is_corresponding":false},{"id":527065,"name":"Craig M. Coopersmith","orcid":"0000-0003-2400-3217","position":6,"is_corresponding":false},{"id":251683,"name":"M. Neale Weitzmann","orcid":"0000-0003-3305-5748","position":7,"is_corresponding":false},{"id":251685,"name":"Roberto Pacifici","orcid":"0000-0001-6077-8250","position":8,"is_corresponding":false},{"id":251679,"name":"Mingcan Yu","orcid":"0009-0001-4221-0829","position":0,"is_corresponding":true}],"reference_count":87,"raw_metadata":null,"created_at":"2026-07-18T23:42:35.448762Z","pmid":"33586672","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}