دورية أكاديمية
Immunoregulatory and lipid presentation pathways are upregulated in human face transplant rejection.
العنوان: | Immunoregulatory and lipid presentation pathways are upregulated in human face transplant rejection. |
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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. |
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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 |
تدمد: | 1558-8238 |
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DOI: | 10.1172/JCI135166 |