单核细胞
巨噬细胞
癌症研究
细胞生物学
化学
内科学
免疫学
医学
生物
体外
生物化学
作者
Collin Z Jordan,Matthew Tunbridge,Irma Husain,Hiroki Kitai,Miriam Dilts,Oscar Fay,Koki Abe,Catherine Xiang,Jean Kwun,Tomokazu Souma,Edward B. Thorp,Xunrong Luo
出处
期刊:PubMed
日期:2024-01-23
标识
DOI:10.1172/jci.insight.178502
摘要
Innate immune cells are important in the initiation and potentiation of alloimmunity in transplantation. Immediately upon organ anastomosis and reperfusion, recipient monocytes enter the graft from circulation and differentiate to inflammatory macrophages to promote allograft inflammation. However, factors that drive their differentiation to inflammatory macrophages are not understood. Here, we showed that the receptor tyrosine kinase AXL was a key driver of early intragraft differentiation of recipient infiltrating monocytes to inflammatory macrophages in the presence of allogeneic stimulation and cell-cell contact. In this context, the differentiated inflammatory macrophages were capable of efficient alloantigen presentation and allo-stimulation of T cells of the indirect pathway. Consequently, early and transient AXL inhibition with the pharmacological inhibitor bemcentinib resulted in a profound reduction of initial allograft inflammation and a significant prolongation of allograft survival in a murine heart transplant model. Our results support further investigation of AXL inhibition as part of an induction regimen for transplantation.
科研通智能强力驱动
Strongly Powered by AbleSci AI