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Vendor-specific microbiome controls both acute and chronic murine lung allograft rejection by altering CD4+ Foxp3+ regulatory T cell levels.
Guo, Yizhan; Wang, Qing; Li, Dongge; Onyema, Oscar Okwudiri; Mei, Zhongcheng; Manafi, Amir; Banerjee, Anirban; Mahgoub, Bayan; Stoler, Mark H; Barker, Thomas H; Wilkes, David S; Gelman, Andrew E; Kreisel, Daniel; Krupnick, Alexander Sasha.
Afiliação
  • Guo Y; Department of Surgery, University of Virginia, Charlottesville, Virginia.
  • Wang Q; Carter Immunology Center, University of Virginia, Charlottesville, Virginia.
  • Li D; Department of Surgery, University of Virginia, Charlottesville, Virginia.
  • Onyema OO; Carter Immunology Center, University of Virginia, Charlottesville, Virginia.
  • Mei Z; Department of Surgery, University of Virginia, Charlottesville, Virginia.
  • Manafi A; Carter Immunology Center, University of Virginia, Charlottesville, Virginia.
  • Banerjee A; Department of Surgery, University of Virginia, Charlottesville, Virginia.
  • Mahgoub B; Carter Immunology Center, University of Virginia, Charlottesville, Virginia.
  • Stoler MH; Department of Surgery, University of Virginia, Charlottesville, Virginia.
  • Barker TH; Carter Immunology Center, University of Virginia, Charlottesville, Virginia.
  • Wilkes DS; Department of Surgery, University of Virginia, Charlottesville, Virginia.
  • Gelman AE; Carter Immunology Center, University of Virginia, Charlottesville, Virginia.
  • Kreisel D; Department of Surgery, University of Virginia, Charlottesville, Virginia.
  • Krupnick AS; Carter Immunology Center, University of Virginia, Charlottesville, Virginia.
Am J Transplant ; 19(10): 2705-2718, 2019 10.
Article em En | MEDLINE | ID: mdl-31278849
ABSTRACT
Despite standardized postoperative care, some lung transplant patients suffer multiple episodes of acute and chronic rejection while others avoid graft problems for reasons that are poorly understood. Using an established model of C57BL/10 to C57BL/6 minor antigen mismatched single lung transplantation, we now demonstrate that the recipient microbiota contributes to variability in the alloimmune response. Specifically, mice from the Envigo facility in Frederick, Maryland contain nearly double the number of CD4+ Foxp3+ regulatory T cells (Tregs ) than mice from the Jackson facility in Bar Harbor, Maine or the Envigo facility in Indianapolis, Indiana (18 vs 9 vs 7%). Lung graft recipients from the Maryland facility thus do not develop acute or chronic rejection. Treatment with broad-spectrum antibiotics decreases Tregs and increases both acute and chronic graft rejection in otherwise tolerant strains of mice. Constitutive depletion of regulatory T cells, using Foxp3-driven expression of diphtheria toxin receptor, leads to the development of chronic rejection and supports the role of Tregs in both acute and chronic alloimmunity. Taken together, our data demonstrate that the microbiota of certain individuals may contribute to tolerance through Treg -dependent mechanisms and challenges the practice of indiscriminate broad-spectrum antibiotic use in the perioperative period.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfócitos T CD4-Positivos / Transplante de Pulmão / Linfócitos T Reguladores / Comércio / Fatores de Transcrição Forkhead / Microbiota / Rejeição de Enxerto / Pneumopatias Tipo de estudo: Etiology_studies / Prognostic_studies Limite: Animals Idioma: En Revista: Am J Transplant Assunto da revista: TRANSPLANTE Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfócitos T CD4-Positivos / Transplante de Pulmão / Linfócitos T Reguladores / Comércio / Fatores de Transcrição Forkhead / Microbiota / Rejeição de Enxerto / Pneumopatias Tipo de estudo: Etiology_studies / Prognostic_studies Limite: Animals Idioma: En Revista: Am J Transplant Assunto da revista: TRANSPLANTE Ano de publicação: 2019 Tipo de documento: Article