title: FOXP3+regulatory T cell ameliorates microvasculature in the rejection of mouse orthotopic tracheal transplants.
abstract: Microvascular loss may be a root cause of chronic rejection in lung transplants, which leads to the bronchiolitis obliterans syndrome. Previous research implicates T regulatory cell (Treg) as a key component of immune modulation, however, Treg has never been examined as a reparative mediator to salvage microvasculature during transplantation. Here, we reconstituted purified Tregs in to allografts, and serially monitored allografts for tissue oxygenation, microvascular perfusion for four weeks. We demonstrated that Tregs reconstitution of allografts significantly improve tissue oxygenation, microvascular flow, epithelial repair, number of CD4+CD25highFOXP3+Tregs, followed by an upregulation of proinflammatory, angiogenic and regulatory genes, while prevented subepithelial deposition of CD4+T cells at d10, and collagen at d28 post-transplantation. Altogether, these findings concluded that Treg-mediated immunotherapy has potential to preserve microvasculature and rescue allograft from sustained hypoxic/ischemic phase, limits airway tissue remodeling, and therefore may be a useful therapeutic tool to prevent chronic rejection after organ transplantation.
authors.affiliation: Organ Transplant Research Section, Comparative Medicine Department, King Faisal Specialist Hospital and Research Centre, MBC 03, P.O. Box 3354, Riyadh 11211, Saudi Arabia. Electronic address: mkhan26@kfshrc.edu.sa.
authors.forename: Mohammad Afzal
authors.initials: MA
authors.lastname: Khan
authors.affiliation: Organ Transplant Research Section, Comparative Medicine Department, King Faisal Specialist Hospital and Research Centre, MBC 03, P.O. Box 3354, Riyadh 11211, Saudi Arabia. Electronic address: falanazi81@kfshrc.edu.sa.
authors.forename: Fatimah
authors.initials: F
authors.lastname: Alanazi
authors.affiliation: Comparative Medicine Department, King Faisal Specialist Hospital and Research Centre, MBC 03, P.O. Box 3354, Riyadh 11211, Saudi Arabia. Electronic address: ahala@kfshrc.edu.sa.
authors.forename: Hala Abdalrahman
authors.initials: HA
authors.lastname: Ahmed
authors.affiliation: Comparative Medicine Department, King Faisal Specialist Hospital and Research Centre, MBC 03, P.O. Box 3354, Riyadh 11211, Saudi Arabia. Electronic address: fmohanna@kfshrc.edu.sa.
authors.forename: Falah Hassan
authors.initials: FH
authors.lastname: Al-Mohanna
authors.affiliation: Comparative Medicine Department, King Faisal Specialist Hospital and Research Centre, MBC 03, P.O. Box 3354, Riyadh 11211, Saudi Arabia. Electronic address: assiri@kfshrc.edu.sa.
authors.forename: Abdullah Mohammed
authors.initials: AM
authors.lastname: Assiri
authors.affiliation: Organ Transplant Research Section, Comparative Medicine Department, King Faisal Specialist Hospital and Research Centre, MBC 03, P.O. Box 3354, Riyadh 11211, Saudi Arabia. Electronic address: dbroering@kfshrc.edu.sa.
authors.forename: Dieter Clemens
authors.initials: DC
authors.lastname: Broering
mesh_terms: D000818:Animals; D051858:Forkhead Transcription Factors / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology*; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D055806:Microvessels / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014132:Trachea / Q000637:transplantation*; D014184:Transplantation, Homologous
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse
keywords: Hypoxia and ischemia; Microvascular repair; Orthotopic tracheal transplants (OTTs); T regulatory cells (Tregs); Tissue pO2