Photo Credit: Big5 Studio

Researchers conducted a retrospective study to offer a thorough single-cell portrayal of lupus nephritis (LN)  kidneys, encompassing immune and non-immune cells, discern disease-linked cell populations, and elucidate their roles within the kidney microenvironment. 

They conducted single-cell RNA and T-cell receptor sequencing on renal biopsy tissues from 40 LN patients and 6 healthy donors for controls. Matched peripheral blood samples from seven LN patients were sequenced. Multiplex immunohistochemical analysis was performed on another cohort of 60 patients, validated by flow cytometric characterization of human kidney tissues and in vitro assays.

The results showed an increase in CD163 ⁺ dendritic cells (DC3s) within the kidneys’ LN, with their abundance positively correlating with the severity of LN. In LN kidneys, DC3s exhibited an activated and highly inflammatory profile, unlike their counterparts in the bloodstream. These kidney-resident DC3s actively interacted with CD4 ² T cells, fueling intrarenal T cell expansion, activating CD4+ effector T cells, and driving polarization towards Th1/Th17 phenotypes. Injured proximal tubular epithelial cells (iPTECs) appeared to play a pivotal role in activating, adhering to, and recruiting DC3s within LN kidneys. Blood DC3s treated with iPTECs displayed distinct capabilities in polarizing Th1/Th17 cells in experimental settings. Quantifying kidney DC3s may be a potential biomarker for assessing induction treatment response in LN patients.

Investigators concluded that the enumeration of renal DC3s represents a promising biomarker for guiding treatment decisions in LN patients, highlighting the complex interplay driving LN pathogenesis.

Source: ard.bmj.com/content/early/2024/01/30/ard-2023-224788