TY - JOUR
T1 - Role of donor macrophages after heart and lung transplantation
AU - Kopecky, Benjamin J.
AU - Frye, Christian
AU - Terada, Yuriko
AU - Balsara, Keki R.
AU - Kreisel, Daniel
AU - Lavine, Kory J.
N1 - Funding Information:
Dr Kopecky was supported by the Principles in Cardiovascular Research Training Grant (T32 HL007081) and the Washington University Physician Scientist Training Program. Dr Lavine is supported by the National Institutes of Health (NIH) K08 HL123519, R01 HL138466, and R01 HL139714, Burroughs Welcome Fund (1014782), Children's Discovery Institute of Washington University and St. Louis Children's Hospital (CH‐II‐2015–462 and CH‐II‐2017–628), and Foundation of Barnes‐Jewish Hospital (8038–88). Dr Liu is supported by NIH R01 HL125655 and HL131908. Dr Kreisel is supported by 1P01AI116501 and R01 HL094601, Veterans Administration Merit Review grant 1I01BX002730, and the Foundation for Barnes‐Jewish Hospital.
Publisher Copyright:
© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons
PY - 2020/5/1
Y1 - 2020/5/1
N2 - Since the 1960s, heart and lung transplantation has remained the optimal therapy for patients with end-stage disease, extending and improving quality of life for thousands of individuals annually. Expanding donor organ availability and immunologic compatibility is a priority to help meet the clinical demand for organ transplant. While effective, current immunosuppression is imperfect as it lacks specificity and imposes unintended adverse effects such as opportunistic infections and malignancy that limit the health and longevity of transplant recipients. In this review, we focus on donor macrophages as a new target to achieve allograft tolerance. Donor organ-directed therapies have the potential to improve allograft survival while minimizing patient harm related to global suppression of recipient immune responses. Topics highlighted include the role of ontogenically distinct donor macrophage populations in ischemia–reperfusion injury and rejection, including their interaction with allograft-infiltrating recipient immune cells and potential therapeutic approaches. Ultimately, a better understanding of how donor intrinsic immunity influences allograft acceptance and survival will provide new opportunities to improve the outcomes of transplant recipients.
AB - Since the 1960s, heart and lung transplantation has remained the optimal therapy for patients with end-stage disease, extending and improving quality of life for thousands of individuals annually. Expanding donor organ availability and immunologic compatibility is a priority to help meet the clinical demand for organ transplant. While effective, current immunosuppression is imperfect as it lacks specificity and imposes unintended adverse effects such as opportunistic infections and malignancy that limit the health and longevity of transplant recipients. In this review, we focus on donor macrophages as a new target to achieve allograft tolerance. Donor organ-directed therapies have the potential to improve allograft survival while minimizing patient harm related to global suppression of recipient immune responses. Topics highlighted include the role of ontogenically distinct donor macrophage populations in ischemia–reperfusion injury and rejection, including their interaction with allograft-infiltrating recipient immune cells and potential therapeutic approaches. Ultimately, a better understanding of how donor intrinsic immunity influences allograft acceptance and survival will provide new opportunities to improve the outcomes of transplant recipients.
KW - basic (laboratory) research/science
KW - heart (allograft) function/dysfunction
KW - heart disease: immune/inflammatory
KW - heart transplantation/cardiology
KW - immunosuppressant
KW - immunosuppression/immune modulation
KW - lung (allograft) function/dysfunction
KW - lung disease: immune/inflammatory
KW - translational research/science
UR - http://www.scopus.com/inward/record.url?scp=85083818708&partnerID=8YFLogxK
U2 - 10.1111/ajt.15751
DO - 10.1111/ajt.15751
M3 - Review article
C2 - 31850651
AN - SCOPUS:85083818708
SN - 1600-6135
VL - 20
SP - 1225
EP - 1235
JO - American Journal of Transplantation
JF - American Journal of Transplantation
IS - 5
ER -