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

ABSTRACT: Bone loss is a frequent but not universal complication of hyperparathyroidism. Using antibiotic-treated or germ-free mice, we show that parathyroid hormone (PTH) only caused bone loss in mice whose microbiota was enriched by the Th17 cell-inducing taxa segmented filamentous bacteria (SFB). SFB+ microbiota enabled PTH to expand intestinal TNF+ T and Th17 cells and increase their S1P-receptor-1 mediated egress from the intestine and recruitment to the bone marrow (BM) that causes bone loss. CXCR3-mediated TNF+ T cell homing to the BM upregulated the Th17 chemoattractant CCL20, which recruited Th17 cells to the BM. This study reveals mechanisms for microbiota-mediated gut-bone crosstalk in mice models of hyperparathyroidism that may help predict its clinical course. Targeting the gut microbiota or T cell migration may represent therapeutic strategies for hyperparathyroidism.

SUBMITTER: Yu M

PROVIDER: S-EPMC6981196 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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

Yu Mingcan M Malik Tyagi Abdul A Li Jau-Yi JY Adams Jonathan J Denning Timothy L TL Weitzmann M Neale MN Jones Rheinallt M RM Pacifici Roberto R

Nature communications 20200124 1

Bone loss is a frequent but not universal complication of hyperparathyroidism. Using antibiotic-treated or germ-free mice, we show that parathyroid hormone (PTH) only caused bone loss in mice whose microbiota was enriched by the Th17 cell-inducing taxa segmented filamentous bacteria (SFB). SFB+ microbiota enabled PTH to expand intestinal TNF+ T and Th17 cells and increase their S1P-receptor-1 mediated egress from the intestine and recruitment to the bone marrow (BM) that ca ...[more]

PMID: 31980603

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