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 show 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-to-cell contact. In this context, the differentiated inflammatory macrophages were capable of efficient alloantigen presentation and allostimulation 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.
Collin Z. Jordan, Matthew Tunbridge, Irma Husain, Hiroki Kitai, Miriam E. Dilts, Olivia K. Fay, Koki Abe, Catherine Xiang, Jean Kwun, Tomokazu Souma, Edward B. Thorp, Xunrong Luo
Usage data is cumulative from January 2024 through September 2024.
Usage | JCI | PMC |
---|---|---|
Text version | 1,093 | 228 |
306 | 86 | |
Figure | 291 | 7 |
Supplemental data | 104 | 3 |
Citation downloads | 57 | 0 |
Totals | 1,851 | 324 |
Total Views | 2,175 |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.