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The Microbial Metabolite Butyrate Stimulates Bone Formation via T Regulatory Cell-Mediated Regulation of WNT10B Expression.
Tyagi, Abdul Malik; Yu, Mingcan; Darby, Trevor M; Vaccaro, Chiara; Li, Jau-Yi; Owens, Joshua A; Hsu, Emory; Adams, Jonathan; Weitzmann, M Neale; Jones, Rheinallt M; Pacifici, Roberto.
Affiliation
  • Tyagi AM; Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University, Atlanta, GA, USA.
  • Yu M; Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University, Atlanta, GA, USA.
  • Darby TM; Department of Pediatrics, Emory University, Atlanta, GA, USA.
  • Vaccaro C; Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University, Atlanta, GA, USA.
  • Li JY; Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University, Atlanta, GA, USA.
  • Owens JA; Department of Pediatrics, Emory University, Atlanta, GA, USA.
  • Hsu E; Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University, Atlanta, GA, USA.
  • Adams J; Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University, Atlanta, GA, USA.
  • Weitzmann MN; Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University, Atlanta, GA, USA; Atlanta VA Medical Center, Decatur, GA, USA.
  • Jones RM; Department of Pediatrics, Emory University, Atlanta, GA, USA.
  • Pacifici R; Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University, Atlanta, GA, USA; Immunology and Molecular Pathogenesis Program, Emory University, Atlanta, GA, USA. Electronic address: roberto.pacifici@emory.edu.
Immunity ; 49(6): 1116-1131.e7, 2018 12 18.
Article de En | MEDLINE | ID: mdl-30446387
ABSTRACT
Nutritional supplementation with probiotics can prevent pathologic bone loss. Here we examined the impact of supplementation with Lactobacillus rhamnosus GG (LGG) on bone homeostasis in eugonadic young mice. Micro-computed tomography revealed that LGG increased trabecular bone volume in mice, which was due to increased bone formation. Butyrate produced in the gut following LGG ingestion, or butyrate fed directly to germ-free mice, induced the expansion of intestinal and bone marrow (BM) regulatory T (Treg) cells. Interaction of BM CD8+ T cells with Treg cells resulted in increased secretion of Wnt10b, a bone anabolic Wnt ligand. Mechanistically, Treg cells promoted the assembly of a NFAT1-SMAD3 transcription complex in CD8+ cells, which drove expression of Wnt10b. Reducing Treg cell numbers, or reconstitution of TCRß-/- mice with CD8+ T cells from Wnt10b-/- mice, prevented butyrate-induced bone formation and bone mass acquisition. Thus, butyrate concentrations regulate bone anabolism via Treg cell-mediated regulation of CD8+ T cell Wnt10b production.
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Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Ostéogenèse / Butyrates / Lymphocytes T régulateurs / Protéines de type Wingless Limites: Animals Langue: En Journal: Immunity Sujet du journal: ALERGIA E IMUNOLOGIA Année: 2018 Type de document: Article Pays d'affiliation: États-Unis d'Amérique Pays de publication: EEUU / ESTADOS UNIDOS / ESTADOS UNIDOS DA AMERICA / EUA / UNITED STATES / UNITED STATES OF AMERICA / US / USA

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Ostéogenèse / Butyrates / Lymphocytes T régulateurs / Protéines de type Wingless Limites: Animals Langue: En Journal: Immunity Sujet du journal: ALERGIA E IMUNOLOGIA Année: 2018 Type de document: Article Pays d'affiliation: États-Unis d'Amérique Pays de publication: EEUU / ESTADOS UNIDOS / ESTADOS UNIDOS DA AMERICA / EUA / UNITED STATES / UNITED STATES OF AMERICA / US / USA