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

Author

Listed:
  • Mingcan Yu

    (Emory University
    Emory University)

  • Abdul Malik Tyagi

    (Emory University
    Emory University)

  • Jau-Yi Li

    (Emory University
    Emory University)

  • Jonathan Adams

    (Emory University
    Emory University)

  • Timothy L. Denning

    (Georgia State University)

  • M. Neale Weitzmann

    (Emory University
    Emory University
    Atlanta VA Medical Center)

  • Rheinallt M. Jones

    (Emory University
    Emory University
    Emory University)

  • Roberto Pacifici

    (Emory University
    Emory University
    Emory University)

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.

Suggested Citation

  • Mingcan Yu & Abdul Malik Tyagi & Jau-Yi Li & Jonathan Adams & Timothy L. Denning & M. Neale Weitzmann & Rheinallt M. Jones & Roberto Pacifici, 2020. "PTH induces bone loss via microbial-dependent expansion of intestinal TNF+ T cells and Th17 cells," Nature Communications, Nature, vol. 11(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-14148-4
    DOI: 10.1038/s41467-019-14148-4
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