Conference Proceeding

FOXP3+ regulatory T cell mediated microvascular recovery in the mouse model of airway allografts

Dr. Mohammad Afzal Khan,
King Faisal Specialist Hospital and Research Centre, Saudi Arabia

Dr. Mohammad Afzal Khan is a Scientist in Organ Transplant Centre, Department of Comparative Medicine at King Faisal Specialist Hospital and Research Center, KSA. From 2013-2014, he was a Assistant Professor at University of Sharjah, UAE. He is a member of several societies International Complement Society, UK, Scientific research advisory board, Onisome HealthCare, India, American Society of Transplantation, USA, American Thoracic Society, USA and Federation of Clinical Immunology Societies, USA.

Microvascular loss may be a root cause of chronic rejection in lung transplants, which leads to the bronchiolitis obliterans syndrome (BOS). Previous research implicates T regulatory cell (Tregs) as a key component of immune modulation. However, Tregs have never been examined as a reparative mediator to rescue microvasculature during allograft rejection. The orthotopic tracheal transplant model is ideal for studying rejection-associated airway hypoxia and ischemia. Here, we reconstituted purified Tregs into allografts and serially monitored allografts for tissue oxygenation, blood flow, and functional microvasculature for the period of four weeks. Our results showed that Tregs prevent deposition of CD4+T cells on vascular endothelial cells and significantly improves oxygenation, blood flow, and epithelial repair at d10, followed by a rise in IL-10, VEGF, and ANGPT2 gene expression, as well as a significant drop in Col1a, Col3a, Col5a genes, and subepithelial deposition of collagen at d10 and d28. In addition, Treg-mediated microvascular reestablishment was abrogated through anti-mCD25-mediated depletion, which accelerates microvasculature loss, low tpO2 and BPUs at d8, and complete loss of microvasculature/acute rejection at d9 compared with at d10 in untreated allografts. These results indicated that Tregs delayed acute rejection and thus shortens the phase of hypoxia and ischemia, which favors allograft recovery. Altogether, these findings demonstrated 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 in designing single/combined Treg therapy to rescue organ rejection in clinical settings.

Published: 28 April 2017