The quest to understand lung transplantation and enhance patient outcomes has led researchers at Washington University School of Medicine in St. Louis to make significant strides. A new study, led by investigators in the Department of Surgery at WashU Medicine, explores groundbreaking insights into the immune system’s interaction with transplanted lung tissues.
The study provides vital data on how regulatory T cells that reside in the transplanted lung can ameliorate graft rejection and promote lung transplant survival.
The study is published March 18 in the Journal of Clinical Investigation.
For the study, WashU Medicine researchers analyzed regulatory Foxp3+ T cells, which play a crucial role in maintaining immune tolerance. The team utilized advanced genomic techniques, including single-cell RNA sequencing, to delve into these cells’ properties and their contributions to immune regulation in lung transplantation.
“Understanding the molecular and cellular mechanisms underlying the immunological acceptance of transplanted lungs is critical in developing more effective treatments for our patients,” said senior author Daniel Kreisel, MD, PhD, the G. Alexander Patterson, MD/Mid-America Transplant Endowed Distinguished Chair in Lung Transplantation.
The team’s use of cutting-edge techniques, including intravital two-photon microscopy, provided a clear visualization of immune processes how regulatory Foxp3+ T cells that are recruited to and reside within the transplanted lung prevent rejection. Significantly, amphiregulin—an endogenous growth factor involved in tissue regeneration—was shown to be produced by these graft-resident regulatory Foxp3+ T cells, suggesting that these cells use multiple pathways that promote graft survival.
“These findings could be ground-breaking in creating new immunosuppressive regimens for lung transplant patients,” notes Kreisel, who is Vice Chair for Research in the Department of Surgery. “As transplanted lungs can be accessed through the airways, our findings could pave the way for novel local therapeutic strategies that enhance the beneficial functions of regulatory Foxp3+ T cells in the graft.”
“Our research aimed to tackle one of the most pressing challenges in lung transplantation—immune rejection. Through our detailed molecular and cellular analysis, we hope to develop strategies that can help lung transplant patients lead longer and healthier lives,” says the study’s first author, Wenjun Li, MD, an associate professor of surgery and director of microsurgery in the Thoracic Immunobiology Laboratory at WashU Medicine.