Single-cell transcriptomics of mouse kidney transplants reveals a potentially novel myeloid cell pathway for transplant rejection

We used a murine kidney transplantation model and single-cell transcriptomics to dissect the contribution of myeloid cell subsets and their potential signaling pathways to kidney transplant rejection. Using a variety of bioinformatic techniques including machine learning, we demonstrated that kidney allograft-infiltrating myeloid cells followed a trajectory of differentiating from monocytes to pro-inflammatory macrophages, and exhibited distinct interactions with kidney allograft parenchymal cells. While this process correlated with a unique pattern of myeloid cell transcripts, a top gene identified was Axl, a member of the receptor tyrosine kinase familyTAM(Tyro3/Axl/Mertk). Kidneys from 6-7 weeks old BALB/c (male or female) mice were transplanted into bilaterally nephrectomized B6 (WT or KO) male recipients. In some of the experiments, kidney allograft tolerance was induced in the recipients by infusions of donor apoptotic cells.