In mouse transplanted hearts, donor CCR2+ macrophages promote allograft rejection, whereas donor CCR2– macrophages promote allograft survival. These findings, published in Circulation, suggest that targeting the innate immune response of donor hearts might be beneficial for transplantation recipients.
Using lineage tracing, single-cell RNA sequencing, cell ablation and conditional gene-deletion strategies, Kopecky and colleagues established that donor macrophages do persist after transplantation of a heart into a recipient mouse and are distinct from recipient-derived cells. Furthermore, CCR2+ and CCR2− macrophage populations are transcriptionally and morphologically distinct. Selective depletion of donor CCR2+ macrophages before transplantation prolonged allograft survival. By contrast, selective depletion of donor CCR2− macrophages reduced allograft survival. Further analysis revealed that CCR2+ macrophages were activated via MYD88–NF-κB signalling, and deletion of Myd88 in donor macrophages reduced the recruitment of antigen-presenting cells, limited the capacity of antigen-presenting cells to present antigen to T cells, decreased the emergence of allograft-reactive T cells and extended survival of the allograft.
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