دورية أكاديمية
Callus γδ T cells and microbe-induced intestinal Th17 cells improve fracture healing in mice.
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) |
References: | BMC Musculoskelet Disord. 2016 Sep 05;17(1):383. (PMID: 27596101) J Bone Joint Surg Am. 2000 Feb;82(2):161-73. (PMID: 10682725) J Clin Invest. 2020 Apr 1;130(4):1767-1781. (PMID: 31917685) J Bone Miner Res. 2015 Jan;30(1):55-63. (PMID: 25043591) Nat Rev Immunol. 2017 Dec;17(12):733-745. (PMID: 28920588) Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10871-6. (PMID: 18663225) J Immunol. 1998 Apr 1;160(7):3513-21. (PMID: 9531313) Cells. 2020 Aug 17;9(8):. (PMID: 32824536) Curr Protoc Mouse Biol. 2015 Mar 02;5(1):35-49. (PMID: 25727199) Proc Natl Acad Sci U S A. 2014 May 6;111(18):6696-701. (PMID: 24753589) Cell. 2015 Oct 8;163(2):367-80. (PMID: 26411289) Methods Mol Biol. 2014;1130:35-44. (PMID: 24482163) J Immunol. 2006 Oct 1;177(7):4662-9. (PMID: 16982905) Immunity. 2009 Oct 16;31(4):677-89. (PMID: 19833089) J Trauma. 1997 May;42(5):895-903; discussion 903-4. (PMID: 9191672) J Hyg Epidemiol Microbiol Immunol. 1987;31(2):219-24. (PMID: 3497192) J Leukoc Biol. 2011 May;89(5):669-73. (PMID: 21208896) N Engl J Med. 2009 Aug 27;361(9):888-98. (PMID: 19710487) Cell Host Microbe. 2008 Oct 16;4(4):337-49. (PMID: 18854238) Front Immunol. 2019 Aug 16;10:1954. (PMID: 31475013) J Immunol Methods. 2015 Jun;421:104-111. (PMID: 25858227) Cell Metab. 2010 Feb 3;11(2):161-71. (PMID: 20142103) J Exp Med. 2006 Nov 27;203(12):2673-82. (PMID: 17088434) Cell Metab. 2015 Nov 3;22(5):799-810. (PMID: 26456334) Cytokine Growth Factor Rev. 2003 Oct;14(5):409-26. (PMID: 12948524) Clin Neuropharmacol. 2010 Mar-Apr;33(2):91-101. (PMID: 20061941) Sci Transl Med. 2013 Mar 20;5(177):177ra36. (PMID: 23515078) Shock. 2009 Oct;32(4):374-8. (PMID: 19295480) J Am Soc Nephrol. 2010 Jun;21(6):974-85. (PMID: 20299360) Eur J Immunol. 2011 Sep;41(9):2539-43. (PMID: 21952814) Proc Natl Acad Sci U S A. 2011 Mar 15;108 Suppl 1:4615-22. (PMID: 20660719) Injury. 2011 Jun;42(6):551-5. (PMID: 21489527) Nat Commun. 2016 Mar 11;7:10928. (PMID: 26965320) Shock. 2003 Mar;19(3):229-37. (PMID: 12630522) PLoS One. 2012;7(9):e44552. (PMID: 22970248) J Immunol. 2010 Nov 1;185(9):5160-8. (PMID: 20870939) Nat Commun. 2020 Jan 24;11(1):468. (PMID: 31980603) Immunity. 2009 Aug 21;31(2):331-41. (PMID: 19682929) Nat Immunol. 2009 May;10(5):514-23. (PMID: 19305396) Biomed Pharmacother. 2020 Dec;132:110831. (PMID: 33022534) Curr Osteoporos Rep. 2018 Apr;16(2):138-145. (PMID: 29508143) Toxicol Sci. 2004 Dec;82(2):656-60. (PMID: 15470231) Trends Immunol. 2015 Dec;36(12):778-787. (PMID: 26596799) Immunol Rev. 2013 Mar;252(1):89-103. (PMID: 23405897) J Bone Miner Res. 2010 Jul;25(7):1658-67. (PMID: 20200958) Proc Natl Acad Sci U S A. 2016 Dec 13;113(50):E8141-E8150. (PMID: 27911839) J Bone Miner Res. 2003 Sep;18(9):1584-92. (PMID: 12968667) Proc Natl Acad Sci U S A. 2011 Jan 25;108(4):1585-90. (PMID: 21209334) J Bone Miner Res. 2014 Sep;29(9):1981-92. (PMID: 24677326) Adv Immunol. 2012;115:45-71. (PMID: 22608255) Proc Natl Acad Sci U S A. 2012 May 1;109(18):7097-102. (PMID: 22511722) Acta Orthop Scand. 1992 Dec;63(6):579-86. (PMID: 1471500) J Orthop Res. 1984;2(1):97-101. (PMID: 6491805) J Leukoc Biol. 2018 Mar;103(3):409-419. (PMID: 29345366) Front Physiol. 2019 Jan 15;9:1962. (PMID: 30697168) Cell Host Microbe. 2017 Nov 8;22(5):697-704.e4. (PMID: 29120746) PLoS One. 2012;7(6):e40044. (PMID: 22768215) J Bone Miner Res. 2011 Jan;26(1):113-24. (PMID: 20641004) Cell Mol Life Sci. 2016 Aug;73(16):3009-33. (PMID: 27038487) Nat Rev Rheumatol. 2015 Jan;11(1):45-54. (PMID: 25266456) J Exp Med. 2007 Nov 26;204(12):2803-12. (PMID: 18025126) J Clin Invest. 2021 Feb 15;131(4):. (PMID: 33586672) Cell. 2004 Jul 23;118(2):229-41. (PMID: 15260992) Annu Rev Immunol. 2009;27:485-517. (PMID: 19132915) Arthritis Rheum. 2009 Jun;60(6):1694-703. (PMID: 19479830) Sci Rep. 2020 Mar 30;10(1):5692. (PMID: 32231224) J Cell Biochem. 2012 Sep;113(9):2895-902. (PMID: 22511335) J Bone Miner Res. 2010 Jul;25(7):1468-86. (PMID: 20533309) Sci Signal. 2008 Mar 25;1(12):pt2. (PMID: 18364513) PeerJ. 2019 Aug 16;7:e7502. (PMID: 31440436) J Clin Invest. 2010 Mar;120(3):883-93. (PMID: 20179354) Shock. 1996 Mar;5(3):202-7. (PMID: 8696984) Expert Opin Drug Saf. 2012 Jan;11(1):15-32. (PMID: 22149454) Br J Pharmacol. 2008 Jul;154(5):1055-62. (PMID: 18454167) Immunity. 2010 Jun 25;32(6):815-27. (PMID: 20620945) Nat Med. 2016 May;22(5):516-23. (PMID: 27019327) J Burn Care Rehabil. 1987 Nov-Dec;8(6):475-82. (PMID: 3125184) Bone. 2014 Jul;64:155-65. (PMID: 24721700) Immunity. 2016 Nov 15;45(5):1078-1092. (PMID: 27851911) Nat Immunol. 2007 Jun;8(6):639-46. (PMID: 17486092) World J Surg. 1996 May;20(4):411-7. (PMID: 8662128) Ann N Y Acad Sci. 2008 Nov;1143:188-211. (PMID: 19076351) Clin Orthop Relat Res. 2003 Sep;(414):95-100. (PMID: 12966282) Transplant Proc. 2001 Feb-Mar;33(1-2):530-1. (PMID: 11266942) J Bone Joint Surg Br. 2008 Aug;90(8):988-94. (PMID: 18669951) Curr Drug Saf. 2018;13(1):26-31. (PMID: 29189175) Cell. 2009 Oct 30;139(3):485-98. (PMID: 19836068) Biochem Biophys Res Commun. 2006 Nov 24;350(3):557-61. (PMID: 17022937) J Biomech. 2009 May 11;42(7):891-7. (PMID: 19281987) J Clin Invest. 2016 Jun 1;126(6):2049-63. (PMID: 27111232) Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14338-43. (PMID: 12376619) Front Immunol. 2018 Jun 26;9:1483. (PMID: 29997627) |
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 |
تدمد: | 1558-8238 |
---|---|
DOI: | 10.1172/JCI166577 |