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Author Notes:

Correspondence: roberto.pacifici@emory.edu

R.M.J., T.L.D., M.N.W., A.G., and R.P. designed the studies. M.Y. developed and optimized protocols, M.Y., A.M.T., J.Y.L., and J.A. performed the research and analyzed the data. R.M.J., T.L.D., M.N.W., and R.P. wrote the paper.

The authors declare no competing interests.

Subjects:

Research Funding:

This study was supported by grants from the National Institutes of Health (RP:DK112946, DK108842, and RR028009; RMJ: DK098391; MNW: AG062334, AR068157 and AR070091).

MNW was also supported by a grant from the Biomedical Laboratory Research & Development Service of the VA Office of Research and Development (5I01BX000105).

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

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

Tools:

Journal Title:

Nature Communications

Volume:

Volume 11, Number 1

Publisher:

, Pages 468-468

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

© 2020, The Author(s).

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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