دورية أكاديمية
أعرض في EDS

Immunoregulatory and lipid presentation pathways are upregulated in human face transplant rejection.

التفاصيل البيبلوغرافية
العنوان: Immunoregulatory and lipid presentation pathways are upregulated in human face transplant rejection.
المؤلفون: Win TS; Department of Dermatology and.; Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Crisler WJ; Department of Dermatology and., Dyring-Andersen B; Department of Dermatology and., Lopdrup R; Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Teague JE; Department of Dermatology and., Zhan Q; Department of Dermatology and., Barrera V; Bioinformatics Core, Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA., Ho Sui S; Bioinformatics Core, Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA., Tasigiorgos S; Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Murakami N; Schuster Transplantation Research Center and., Chandraker A; Schuster Transplantation Research Center and., Tullius SG; Division of Transplant Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Pomahac B; Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA., Riella LV; Schuster Transplantation Research Center and., Clark RA; Department of Dermatology and.
المصدر: The Journal of clinical investigation [J Clin Invest] 2021 Apr 15; Vol. 131 (8).
نوع المنشور: Clinical Trial; Journal Article; Multicenter Study; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; 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: Print 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: Antigen Presentation* , Facial Transplantation* , Gene Expression Profiling* , Receptors, Antigen, T-Cell*/genetics , Receptors, Antigen, T-Cell*/immunology, Graft Rejection/*immunology , Lipids/*immunology , Skin/*immunology , T-Lymphocytes/*immunology, Female ; Follow-Up Studies ; Graft Rejection/genetics ; Graft Rejection/pathology ; Humans ; Male ; Prospective Studies ; Skin/pathology
مستخلص: BACKGROUNDRejection is the primary barrier to broader implementation of vascularized composite allografts (VCAs), including face and limb transplants. The immunologic pathways activated in face transplant rejection have not been fully characterized.METHODSUsing skin biopsies prospectively collected over 9 years from 7 face transplant patients, we studied rejection by gene expression profiling, histology, immunostaining, and T cell receptor sequencing.RESULTSGrade 1 rejection did not differ significantly from nonrejection, suggesting that it does not represent a pathologic state. In grade 2, there was a balanced upregulation of both proinflammatory T cell activation pathways and antiinflammatory checkpoint and immunomodulatory pathways, with a net result of no tissue injury. In grade 3, IFN-γ-driven inflammation, antigen-presenting cell activation, and infiltration of the skin by proliferative T cells bearing markers of antigen-specific activation and cytotoxicity tipped the balance toward tissue injury. Rejection of VCAs and solid organ transplants had both distinct and common features. VCA rejection was uniquely associated with upregulation of immunoregulatory genes, including SOCS1; induction of lipid antigen-presenting CD1 proteins; and infiltration by T cells predicted to recognize CD1b and CD1c.CONCLUSIONOur findings suggest that the distinct features of VCA rejection reflect the unique immunobiology of skin and that enhancing cutaneous immunoregulatory networks may be a useful strategy in combatting rejection.Trial registrationClinicalTrials.gov NCT01281267.FUNDINGAssistant Secretary of Defense and Health Affairs, through Reconstructive Transplant Research (W81XWH-17-1-0278, W81XWH-16-1-0647, W81XWH-16-1-0689, W81XWH-18-1-0784, W81XWH-1-810798); American Society of Transplantation's Transplantation and Immunology Research Network Fellowship Research Grant; Plastic Surgery Foundation Fellowship from the American Society of Plastic Surgeons; Novo Nordisk Foundation (NNF15OC0014092); Lundbeck Foundation; Aage Bangs Foundation; A.P. Moller Foundation for the Advancement of Medical Science; NIH UL1 RR025758.
References: Sci Transl Med. 2015 Mar 18;7(279):279ra39. (PMID: 25787765)
Nat Rev Immunol. 2014 May;14(5):289-301. (PMID: 24722477)
PLoS Med. 2009 Jul 21;6(7):e1000097. (PMID: 19621072)
Sci Transl Med. 2015 Jan 7;7(269):269rv1. (PMID: 25568072)
Ann Surg. 2018 Aug;268(2):260-270. (PMID: 29489486)
Curr Opin Organ Transplant. 2015 Dec;20(6):596-601. (PMID: 26536419)
J Clin Invest. 2018 Oct 1;128(10):4669-4681. (PMID: 30198907)
BMC Bioinformatics. 2020 Jan 28;21(1):30. (PMID: 31992186)
J Exp Med. 1979 Aug 1;150(2):322-37. (PMID: 379265)
Am J Transplant. 2018 Jul;18(7):1804-1809. (PMID: 29723921)
J Invest Dermatol. 1996 Sep;107(3):377-83. (PMID: 8751974)
Nucleic Acids Res. 2009 Jan;37(Database issue):D1006-12. (PMID: 18978023)
Transpl Int. 2011 Aug;24(8):760-9. (PMID: 21554424)
Am J Transplant. 2017 Dec;17(12):3228-3235. (PMID: 28742936)
J Exp Med. 2011 Sep 26;208(10):2055-67. (PMID: 21893603)
Transplantation. 2015 Dec;99(12):2644-50. (PMID: 25989498)
Front Immunol. 2015 Apr 21;6:183. (PMID: 25954276)
Am J Transplant. 2016 Nov;16(11):3305-3307. (PMID: 27457067)
Eur J Immunol. 1997 Dec;27(12):3492-8. (PMID: 9464839)
Blood. 2009 Nov 5;114(19):4099-107. (PMID: 19706884)
F1000Res. 2017 Oct 30;6:1909. (PMID: 29152228)
Am J Transplant. 2008 Jul;8(7):1396-400. (PMID: 18444912)
Plast Reconstr Surg. 2006 Mar;117(3):864-72; discussion 873-5. (PMID: 16525277)
Genome Biol. 2014;15(12):550. (PMID: 25516281)
Curr Opin Organ Transplant. 2018 Feb;23(1):28-33. (PMID: 29189293)
Blood. 2007 Jan 1;109(1):194-202. (PMID: 16968902)
Am J Transplant. 2011 Jun;11(6):1340. (PMID: 21645261)
Curr Opin Immunol. 1993 Oct;5(5):794-9. (PMID: 8240742)
Nat Immunol. 2013 Oct;14(10):978-85. (PMID: 24048119)
Nature. 2017 Jul 6;547(7661):94-98. (PMID: 28636589)
Am J Transplant. 2016 Jul;16(7):2158-71. (PMID: 26749226)
J Invest Dermatol. 2010 Feb;130(2):362-70. (PMID: 19675575)
J Immunol. 2006 Apr 1;176(7):4431-9. (PMID: 16547281)
Am J Clin Dermatol. 2018 Jun;19(3):345-361. (PMID: 29256113)
J Am Soc Nephrol. 2017 Feb;28(2):575-585. (PMID: 27609616)
J Immunol. 2015 Apr 1;194(7):3475-86. (PMID: 25725111)
Cold Spring Harb Protoc. 2011 Jun 01;2011(6):595-603. (PMID: 21632786)
Science. 1993 May 14;260(5110):920-6. (PMID: 8493529)
N Engl J Med. 2010 Oct 7;363(15):1451-62. (PMID: 20925547)
Am J Transplant. 2017 Jul;17(7):1935-1940. (PMID: 28141920)
Methods Mol Biol. 2004;248:27-49. (PMID: 14970490)
Curr Opin Organ Transplant. 2011 Feb;16(1):47-53. (PMID: 21157342)
Transpl Int. 2018 Jul;31(7):677-688. (PMID: 29421860)
Transpl Int. 2016 Jun;29(6):663-71. (PMID: 26841362)
Am J Transplant. 2010 May;10(5):1200-9. (PMID: 20353468)
معلومات مُعتمدة: P30 AR069625 United States AR NIAMS NIH HHS; K08 DK120868 United States DK NIDDK NIH HHS; T32 AR007098 United States AR NIAMS NIH HHS; U01 AI132898 United States AI NIAID NIH HHS; R01 AG064165 United States AG NIA NIH HHS; UL1 RR025758 United States RR NCRR NIH HHS
فهرسة مساهمة: Keywords: Adaptive immunity; Cellular immune response; Immunology; Transplantation
سلسلة جزيئية: ClinicalTrials.gov NCT01281267
المشرفين على المادة: 0 (Lipids)
0 (Receptors, Antigen, T-Cell)
تواريخ الأحداث: Date Created: 20210305 Date Completed: 20210928 Latest Revision: 20231014
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC8262560
DOI: 10.1172/JCI135166
PMID: 33667197
قاعدة البيانات: MEDLINE
الوصف
تدمد:1558-8238
DOI:10.1172/JCI135166