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

• Authors: Mingcan Yu, Emory University; Abdul Malik Tyagi, Emory University; Jau-Yi Li, Emory University; Jonathan Adams, Emory University; Timothy L. Denning, Georgia State University; M. Neale Weitzmann, Emory University; Rheinallt Jones, Emory University; Roberto Pacifici, Emory University
• Journal Title: Nature Communications
• Volume: Volume 11, Number 1
• Publisher: Nature Publishing Group | 2020-01-24, Pages 468-468
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1038/s41467-019-14148-4
• Subjects: Biology, Microbiology; Health Sciences, Immunology; Health Sciences, Nutrition; Biology, Molecular
• Keywords: Science & Technology; Multidisciplinary Sciences; Science & Technology - Other Topics; Segmented filamentous bacteria; Anabolic activity; Parathyroid hormone; PTH/PTHRP Receptor; T(H)17 Cells; Intermittent; Secondary; Disease; Beta; Hyperparathyroidism

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.