Pro-angiogenic effects of kidney-infiltrating neutrophils: allies or adversaries in UV-induced skin-kidney axis? 2788

Abstract Description Immune crosstalk between injured and distal organs has been associated with both inflammatory and tissue repair mechanisms at distal sites. We previously showed that skin injury by ultraviolet (UV) light stimulates neutrophil migration to the kidney and increases expression of renal injury genes. To define the mechanism of neutrophil-mediated skin-kidney crosstalk, we applied single-cell RNAseq on saline-perfused digested kidneys and Ly6G-enriched neutrophils of B6 mice, prior to and 2 days after UVB. We found acute skin exposure to UV results in an expansion of renal glomerular but not tubular endothelial cells, confirmed by CD31 staining. The most highly upregulated pathways in the expanded glomerular endothelial cluster were regulation of angiogenesis and vascular development, which were validated by increased angiogenesis transcriptional scores and expression of Angpt2, Angptl1, and Angptl4 genes by qPCR. Neutrophil scRNAseq and flow cytometry analyses revealed intra-renal infiltration of pro-angiogenic neutrophils (Vegfr1+). This skin-kidney axis is relevant to lupus patients, for whom skin exposure to UV can worsen kidney disease. Spatial transcriptomics analysis of lupus patient kidney biopsies revealed increased intra-glomerular neutrophils in patients with active skin disease and a correlation between ANGPTL pathway activity and neutrophil presence. These studies present a novel model by which neutrophils may mediate renal angiogenesis secondary to acute skin injury. Funding Sources Dartmouth Hitchcock Lupus Fund Hitchcock Foundation Dartmouth Center for Quantitative Biology Department of Defense Lupus Research Program Topic Categories Computational and Systems Immunology (COMP)