دورية أكاديمية
أعرض في EDS

Callus γδ T cells and microbe-induced intestinal Th17 cells improve fracture healing in mice.

التفاصيل البيبلوغرافية
العنوان: Callus γδ T cells and microbe-induced intestinal Th17 cells improve fracture healing in mice.
المؤلفون: Dar HY; Division of Endocrinology, Metabolism and Lipids, Department of Medicine and.; Emory Microbiome Research Center, Emory University, Atlanta, Georgia, USA., Perrien DS; Division of Endocrinology, Metabolism and Lipids, Department of Medicine and.; Emory Microbiome Research Center, Emory University, Atlanta, Georgia, USA., Pal S; Division of Endocrinology, Metabolism and Lipids, Department of Medicine and.; Emory Microbiome Research Center, Emory University, Atlanta, Georgia, USA., Stoica A; Division of Endocrinology, Metabolism and Lipids, Department of Medicine and.; Emory Microbiome Research Center, Emory University, Atlanta, Georgia, USA., Uppuganti S; Department of Orthopedic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA., Nyman JS; Department of Orthopedic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, USA.; Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee, USA., Jones RM; Emory Microbiome Research Center, Emory University, Atlanta, Georgia, USA.; Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Emory University, Atlanta, Georgia, USA., Weitzmann MN; Division of Endocrinology, Metabolism and Lipids, Department of Medicine and.; Emory Microbiome Research Center, Emory University, Atlanta, Georgia, USA.; Atlanta VA Health Care System, Department of Veterans Affairs, Decatur, Georgia, USA., Pacifici R; Division of Endocrinology, Metabolism and Lipids, Department of Medicine and.; Emory Microbiome Research Center, Emory University, Atlanta, Georgia, USA.; Immunology and Molecular Pathogenesis Program, Emory University, Atlanta, Georgia, USA.
المصدر: The Journal of clinical investigation [J Clin Invest] 2023 Apr 17; Vol. 133 (8). Date of Electronic Publication: 2023 Apr 17.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.
اللغة: English
بيانات الدورية: Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 7802877 Publication Model: Electronic Cited Medium: Internet ISSN: 1558-8238 (Electronic) Linking ISSN: 00219738 NLM ISO Abbreviation: J Clin Invest Subsets: MEDLINE
أسماء مطبوعة: Publication: 1999- : Ann Arbor, MI : American Society for Clinical Investigation
Original Publication: New Haven [etc.] American Society for Clinical Investigation.
مواضيع طبية MeSH: Th17 Cells* , Microbiota*, Mice ; Animals ; Fracture Healing ; Mice, Inbred C57BL ; Receptors, Antigen, T-Cell, gamma-delta/genetics
مستخلص: IL-17A (IL-17), a driver of the inflammatory phase of fracture repair, is produced locally by several cell lineages including γδ T cells and Th17 cells. However, the origin of these T cells and their relevance for fracture repair are unknown. Here, we show that fractures rapidly expanded callus γδ T cells, which led to increased gut permeability by promoting systemic inflammation. When the microbiota contained the Th17 cell-inducing taxon segmented filamentous bacteria (SFB), activation of γδ T cells was followed by expansion of intestinal Th17 cells, their migration to the callus, and improved fracture repair. Mechanistically, fractures increased the S1P receptor 1-mediated (S1PR1-mediated) egress of Th17 cells from the intestine and enhanced their homing to the callus through a CCL20-mediated mechanism. Fracture repair was impaired by deletion of γδ T cells, depletion of the microbiome by antibiotics (Abx), blockade of Th17 cell egress from the gut, or Ab neutralization of Th17 cell influx into the callus. These findings demonstrate the relevance of the microbiome and T cell trafficking for fracture repair. Modifications of microbiome composition via Th17 cell-inducing bacteriotherapy and avoidance of broad-spectrum Abx may represent novel therapeutic strategies to optimize fracture healing.
التعليقات: Comment in: Nat Rev Rheumatol. 2023 May;19(5):258. (PMID: 37020106)
Comment in: J Clin Invest. 2023 Apr 17;133(8):. (PMID: 37066879)
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معلومات مُعتمدة: R01 DK112946 United States DK NIDDK NIH HHS; S10 RR028009 United States RR NCRR NIH HHS; U54 AG062334 United States AG NIA NIH HHS; R01 AR079298 United States AR NIAMS NIH HHS; R01 DK119229 United States DK NIDDK NIH HHS; R01 DK124821 United States DK NIDDK NIH HHS; R01 AR080750 United States AR NIAMS NIH HHS; R01 AR073874 United States AR NIAMS NIH HHS; I01 BX005062 United States BX BLRD VA; I01 BX005852 United States BX BLRD VA; R01 AR068157 United States AR NIAMS NIH HHS; R01 AR070091 United States AR NIAMS NIH HHS; I01 BX000105 United States BX BLRD VA; R01 DK098391 United States DK NIDDK NIH HHS
فهرسة مساهمة: Keywords: Bone Biology; Bone disease; Microbiology; Orthopedics; T cells
المشرفين على المادة: 0 (Receptors, Antigen, T-Cell, gamma-delta)
تواريخ الأحداث: Date Created: 20230307 Date Completed: 20230418 Latest Revision: 20240519
رمز التحديث: 20240519
مُعرف محوري في PubMed: PMC10104897
DOI: 10.1172/JCI166577
PMID: 36881482
قاعدة البيانات: MEDLINE
الوصف
تدمد:1558-8238
DOI:10.1172/JCI166577