Microvascular immunity is organ-specific and remodeled after kidney injury

Blood tests are a common method for diagnosing and monitoring various health conditions. Nevertheless, the extent to which blood analysis can offer insights into immune and organ dysfunction remains uncertain. Here, we conducted a comprehensive analysis of blood-borne leukocytes in the vasculature of different mouse organs and compared it to peripheral blood and parenchymal samples. We observed that microvascular immune cells outnumber tissue-resident counterparts in the kidney, liver and lung. Here, classical monocytes and lymphocytes are diminished while nonclassical and SSC-high monocytes are enriched compared to blood. Utilizing single-cell sequencing, we identified specific cell populations up to 100-fold expanded in the kidney vasculature including macrophages, plasmacytoid dendritic cells, B cells, and innate lymphoid cells type 2. Microvascular enrichment can trigger a local phenotype switch as shown in B cells specifically dwelling in glomerular capillaries. Peritonitis and acute kidney injury (AKI) elicited a multifaceted and systemic response of microvascular leukocytes independent of tissue infiltration. It involves remote organ effects, such as a 16-fold increase of leukocytes in the splenic circulation or 64-fold increase of SSC-high monocytes in the liver circulation that is not detectable in peripheral blood. Following full recovery from AKI, persistent changes were observed particularly in the renal vasculature, while most leukocytes in the peripheral blood have already returned to baseline levels. Collectively, our findings suggest a paradigm of organ- and disease-specific microvascular immunity that largely eludes conventional blood and tissue analysis. We examined the single-cell transcriptomes of kidney tissue, renal microcirculation and peripheral blood from four untreated and four IRI-reg mice. For this purpose, single-cell suspensions were prepared from fresh tissue and peripheral blood material, labeled with sample tags (BD CTT Mouse Single Cell Multiplexing Kit) and were then subjected to microwell-based single-cell RNA sequencing (scRNA-seq) using BD Rhapsody Express system by BD Biosciences following manufacturer’s instructions. Samples were sequenced using the Illumina NovaSeq and analyzed using SevenBridges. Single-cell capture was performed using the BD Rhapsody Express following manufacturer’s instructions.