A major challenge in developing treatments for lupus, an autoimmune disease that affects many organs in the human body, has been in identifying disease-specific cell types and their state and function. This webcast will describe how we profiled immune cells infiltrating the lupus kidneys. Using single-cell RNAseq (scRNAseq), we found 21 immune cell types in the lupus kidney that were mostly absent in healthy kidney. We focused on three monocytes, whose gene-expression signatures implied they represented a continuum of states. First, monocytes enter from the blood; in the tissue they differentiate to a phagocytic form, before finally turning into a reparative state. Importantly, these monocytes did not map to those in prior studies, suggesting disease and tissue specificity. Kidney is a complex but highly organized tissue. We hypothesized that the monocytes were changing state in response to environmental signals. Since spatial relationships are lost after tissue dissociation required for scRNA-seq, we instead used intact clinical specimens to map the monocytes’ relationships to histological features. We found that each monocyte state occupies a discrete renal compartment, suggesting that each compartment provides a unique set of disease- and tissue-specific signals for monocyte differentiation in the lupus kidney.

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This webcast will feature:

• Functional insights into lupus-specific monocyte states in tissue.
• How we used RNAscope in situ technologies to stain state-specific monocyte cell types in tissue.
• How we related monocyte states to histological features of complex tissue.