A Gene-expression Module Identifies Circulating Immune Cells with Enhanced Recruitment to Sites of Inflammation

Circulating immune cells are critical mediators of the response to inflammation upon recruitment to the tissue but how gene expression state influences recruitment is not well known. Here we report the longitudinal single-cell transcriptome profiling of blood mononuclear cells in patients undergoing kidney transplantation rejection. We identify a gene expression module which is associated to transcriptional regulation, homing and early activation in multiple cell types. The circulating cells expressing this module are reduced in patients undergoing graft rejection. This reduction was confirmed in a pig model of acute kidney transplantation rejection. In connection with this, the module expression drastically increased in the kidney grafts undergoing rejection indicating a preferential recruitment of cells highly expressing this module. We identify the receptor CXCR4 within the module and its ligand CXCL12 expressed in the graft as a likely recruitment mechanism between circulating cells and the tissue. We then explore publicly available transcriptomics data in circulating cells and show that this module is generally expressed in healthy individuals and more importantly is associated with the response to infection, including SARS Covid-19. Moreover, we find that module expression is predictive of immune mediated diseases. In summary, we find a gene expression module in circulating immune cells which enables preferential recruitment to inflamed tissues to mediate effector function. Additional metadata information related to the fastq files is available here: https://doi.org/10.5281/zenodo.17611352