Single-cell RNA sequencing (scRNA-seq) is increasingly being used to define cellular phenotypes based on signatures of gene expression. Using this technique, Nir Hacohen, Betty Diamond and colleagues mapped immune cell subsets in the kidneys of patients with lupus nephritis.
The researchers applied scRNA-seq to cells isolated from kidney biopsy samples collected from 24 patients with lupus nephritis and 10 control samples from living donors. The gene expression data defined kidney cell clusters, including B cells, T cells, natural killer (NK) cells, myeloid cells and epithelial cells. CXCR4 was expressed in the majority of infiltrating kidney cells, whereas CX3CR1 was expressed in most myeloid and NK cells.
B cells from lupus nephritis samples ranged from naive to activated cells, but were rare in control kidneys. In addition, the expression of cytotoxic molecules and specific lineage markers identified clusters of NK cells and CD8+ T cells. Exhaustion markers were expressed at higher levels in blood CD8+ T cells than in kidney CD8+ T cells. CD4+ memory T cells were present in both patients and controls, but patient samples had a larger central memory CD4+ T cell population and higher expression of interferon-stimulated genes (ISGs).
The main myeloid cell cluster in control samples likely represented resident kidney cells and its unique gene expression pattern differed from that of peripheral cell subsets. In patient samples, this myeloid cell cluster expressed higher levels of ISGs and anti-inflammatory genes than in controls. Other myeloid cells identified in patient samples included a cluster of inflammatory cells most similar to CD16+ blood monocytes, and cells that either expressed markers of alternative activation or of the dendritic cell lineage.
The gene expression profile of immune cells isolated from the urine of patients with lupus nephritis revealed a high correlation with the gene signature of kidney immune cells. Isolating immune cells from urine might thus serve as a noninvasive method for the analysis of kidney immune cells.
Arazi, A. et al. The immune cell landscape in kidneys of patients with lupus nephritis. Nat. Immunol. 20, 902–914 (2019)
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Wang, M. Gene signatures reveal kidney immune cells. Nat Rev Nephrol 15, 528 (2019). https://doi.org/10.1038/s41581-019-0179-7