Understanding Innate Immunity in Lung Transplantation

Although lung transplantation surgery provides the best path for patients with severe lung conditions to return to daily activities and regain their health, obstacles such as the body’s own immune system stand in the way of success after this complex, life-saving procedure.

Investigators within the Washington University Department of Surgery are doing critical research to understand the immunological processes that can lead to severe complications after lung transplant surgery, including primary graft dysfunction.    

General Surgery residents and leaders of the Thoracic Immunobiology Laboratory collaborated to discuss the body’s innate immune responses that could lead to lung injury and allograft failure in a study published in The Journal of Heart and Lung Transplantation.

When a patient undergoes an organ transplant, the body’s immune system may attack the new graft to protect the body from infection. This can lead the body to reject the new organ.

“Innate immune responses immediately following reperfusion, or restoring blood flow to the transplanted lung, play a critical role in the development of primary lung dysfunction,” says study author and General Surgery lab resident Hailey Shepherd, MD. “This ultimately affects up to 80% of lung recipients and remains the leading cause of death in the first month after pulmonary transplantation.”

Following lung transplantation, a patient will receive antirejection medications that work to suppress the immune system and prevent the body from attacking the new organ.

“Our review focuses on the pathways involved in the innate immune response following lung transplantation,” says co-author and General Surgery resident Jason Gauthier, MD. “Specifically, we discuss the primary mechanisms responsible for an early compromise of cell integrity within the graft or organ that can trigger graft injury and failure.”

The body’s alloimmune response following lung transplantation and pulmonary innate immunity are two major focus areas of the Thoracic Immunobiology Laboratory, led by study co-authors Andrew Gelman, PhD, Daniel Kreisel, MD, PhD, and cross-institutional collaborator and University of Maryland Associate Professor Alexander S. Krupnick, MD. Associate Professor of Surgery Wenjun Li, MD, a member of the Thoracic Immunobiology Laboratory, also contributed to this review.

“After lung transplantation, both apoptotic (programmed) and non- apoptotic cell death occurs,” says Gelman, who is the Jacqueline G. and William E. Maritz Endowed Chair in Immunology and Oncology and professor of cardiothoracic surgery. “Inflammatory cell death leads to the release of endogenous ligands that propagate inflammatory responses through activation of innate immune signaling pathways.”

Kreisel, the inaugural G. Alexander Patterson, MD/Mid-America Transplant Endowed Distinguished Chair in Lung Transplantation, professor of surgery, pathology and immunology, and surgical director of the Lung Transplant Program at Barnes-Jewish Hospital, shares that insight into these mechanisms will help future researchers develop pathways to prevent these immunologic responses from occurring and help improve transplantation outcomes.