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Cited by 148Gut microbiota and healthBone Metabolism and DiseasesT-cell and B-cell Immunology

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

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Yu, Mingcan, Malik Tyagi, Abdul, Li, Jau-Yi, Adams, Jonathan, Denning, Timothy L., Weitzmann, M. Neale, Jones, Rheinallt M., Pacifici, Roberto·2020·Nature Communications
DOI 10.1038/s41467-019-14148-4PMC PMC6981196
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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.

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Cited by

Sorted by citations

Authors
Yu, M., Malik Tyagi, A., Li, J.-Y., Adams, J., Denning, T. L., Weitzmann, M. N., Jones, R. M., & Pacifici, R.
Affiliations
  • Emory University (US)
  • Georgia State University (US)
Corresponding author
Pacifici, Roberto
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2020-01-24
Volume
11
Issue
1
Pages
468-468
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-019-14148-4
PMC
PMC6981196
OpenAlex
W3002574702
Cited by
148
References
6
Citations by year
2026: 26 · 2025: 19 · 2024: 23 · 2023: 25 · 2022: 14 · 2021: 28 · 2020: 12 · 2018: 1
FWCI
6.41
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
U.S. Department of Health & Human Services | National Institutes of Health (DK112946, DK108842, RR028009, DK098391, AG062334)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords
parathyroid hormone, hyperparathyroidism, bone loss, gut microbiota, segmented filamentous bacteria, Th17 cells, intestinal T cells, S1P1 receptor, CXCR3, CCL20, bone marrow homing, germ-free mice, antibiotic-treated mice
MeSH terms
Gastrointestinal Microbiome, Fecal Microbiota Transplantation, Animals, Female, Germ-Free Life, Intestines, Mice, Inbred C57BL, Osteoporosis, Parathyroid Hormone, Tumor Necrosis Factor-alpha, T-Lymphocyte Subsets, Gram-Positive Endospore-Forming Rods, Mice, Knockout, Hyperparathyroidism, Primary, Mice, Th17 Cells

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