Ovariectomy induces bone loss via microbial-dependent trafficking of intestinal TNF+ T cells and Th17 cells.

Autor:	Yu M; Division of Endocrinology, Metabolism and Lipids, Department of Medicine and.; Emory Microbiome Research Center, Emory University, Atlanta, Georgia, USA., Pal S; Division of Endocrinology, Metabolism and Lipids, Department of Medicine and.; Emory Microbiome Research Center, Emory University, Atlanta, Georgia, USA., Paterson CW; Department of Surgery and Emory Critical Care Center, Emory University School of Medicine, Atlanta, Georgia, USA.; Medical Corps, United States Navy, NROTC, Atlanta, Georgia, USA., Li JY; Division of Endocrinology, Metabolism and Lipids, Department of Medicine and.; Emory Microbiome Research Center, Emory University, Atlanta, Georgia, USA., Tyagi AM; Division of Endocrinology, Metabolism and Lipids, Department of Medicine and.; Emory Microbiome Research Center, Emory University, Atlanta, Georgia, USA., Adams J; Division of Endocrinology, Metabolism and Lipids, Department of Medicine and.; Emory Microbiome Research Center, Emory University, Atlanta, Georgia, USA., Coopersmith CM; Emory Microbiome Research Center, Emory University, Atlanta, Georgia, USA.; Department of Surgery and Emory Critical Care Center, Emory University School of Medicine, Atlanta, Georgia, USA., Weitzmann MN; Division of Endocrinology, Metabolism and Lipids, Department of Medicine and.; Emory Microbiome Research Center, Emory University, Atlanta, Georgia, USA.; Atlanta VA Medical Center, Decatur, Georgia, USA., Pacifici R; Division of Endocrinology, Metabolism and Lipids, Department of Medicine and.; Emory Microbiome Research Center, Emory University, Atlanta, Georgia, USA.; Immunology and Molecular Pathogenesis Program, Emory University, Atlanta, Georgia, USA.
Jazyk:	angličtina
Zdroj:	The Journal of clinical investigation [J Clin Invest] 2021 Feb 15; Vol. 131 (4).
DOI:	10.1172/JCI143137
Abstrakt:	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.
Databáze:	MEDLINE
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