{"title":"Update on the immunological mechanisms of primary graft dysfunction and chronic lung allograft dysfunction.","authors":"Jong Cheol Jeong, Andrew E Gelman, Anita S Chong","doi":"10.1097/MOT.0000000000001175","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose of review: </strong>Primary graft dysfunction (PGD) and chronic lung allograft dysfunction (CLAD) are the leading causes of graft loss in lung transplant recipients. The development of mouse lung transplant models has allowed for the genetic dissection of cellular and molecular pathways that prevent graft survival. This review provides an overview into recent mechanistic insights into PGD and CLAD.</p><p><strong>Recent findings: </strong>Mouse orthotopic lung transplant models and investigations of human lung transplant recipeints have revealed new molecular and cellular targets that promote PGD and CLAD. Donor and recipient-derived innate immune cells promote PGD and CLAD. PGD is driven by communication between classical monocytes and tissue-resident nonclassical monocytes activating alveolar macrophages to release chemokines that recruit neutrophils. Products of cell damage trigger neutrophil NET release, which together with NK cells, antibodies and complement, that further promote PGD. The development of CLAD involves circuits that activate B cells, CD8 + T cells, classical monocytes, and eosinophils.</p><p><strong>Summary: </strong>Effective targeted management of PGD and CLAD in lung transplant recipient to improve their long-term outcome remains a critical unmet need. Current mechanistic studies and therapeutic studies in mouse models and humans identify new possibilities for prevention and treatment.</p>","PeriodicalId":10900,"journal":{"name":"Current Opinion in Organ Transplantation","volume":" ","pages":"412-419"},"PeriodicalIF":1.8000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537820/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Opinion in Organ Transplantation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/MOT.0000000000001175","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/16 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"TRANSPLANTATION","Score":null,"Total":0}
引用次数: 0
Abstract
Purpose of review: Primary graft dysfunction (PGD) and chronic lung allograft dysfunction (CLAD) are the leading causes of graft loss in lung transplant recipients. The development of mouse lung transplant models has allowed for the genetic dissection of cellular and molecular pathways that prevent graft survival. This review provides an overview into recent mechanistic insights into PGD and CLAD.
Recent findings: Mouse orthotopic lung transplant models and investigations of human lung transplant recipeints have revealed new molecular and cellular targets that promote PGD and CLAD. Donor and recipient-derived innate immune cells promote PGD and CLAD. PGD is driven by communication between classical monocytes and tissue-resident nonclassical monocytes activating alveolar macrophages to release chemokines that recruit neutrophils. Products of cell damage trigger neutrophil NET release, which together with NK cells, antibodies and complement, that further promote PGD. The development of CLAD involves circuits that activate B cells, CD8 + T cells, classical monocytes, and eosinophils.
Summary: Effective targeted management of PGD and CLAD in lung transplant recipient to improve their long-term outcome remains a critical unmet need. Current mechanistic studies and therapeutic studies in mouse models and humans identify new possibilities for prevention and treatment.
期刊介绍:
Current Opinion in Organ Transplantation is an indispensable resource featuring key, up-to-date and important advances in the field from around the world. Led by renowned guest editors for each section, every bimonthly issue of Current Opinion in Organ Transplantation delivers a fresh insight into topics such as stem cell transplantation, immunosuppression, tolerance induction and organ preservation and procurement. With 18 sections in total, the journal provides a convenient and thorough review of the field and will be of interest to researchers, surgeons and other healthcare professionals alike.