Single-cell analysis identifies the interaction of altered renal tubules with basophils orchestrating kidney fibrosis

Inflammation is an important component of fibrosis but immune processes that orchestrate kidney fibrosis are not well understood. Here we apply single-cell sequencing to a mouse model of kidney fibrosis. We identify a subset of kidney tubule cells with a profibrotic-inflammatory phenotype characterized by the expression of cytokines and chemokines associated with immune cell recruitment. Receptor-ligand interaction analysis and experimental validation indicate that CXCL1 secreted by profibrotic tubules recruits CXCR2(+) basophils. In mice, these basophils are an important source of interleukin-6 and recruitment of the T(H)17 subset of helper T cells. Genetic deletion or antibody-based depletion of basophils results in reduced renal fibrosis. Human kidney single-cell, bulk gene expression and immunostaining validate a function for basophils in patients with kidney fibrosis. Collectively, these studies identify basophils as contributors to the development of renal fibrosis and suggest that targeting these cells might be a useful clinical strategy to manage chronic kidney disease. How fibrosis and inflammation are integrated is not entirely clear. Here the authors show that profibrotic proximal tubular cells in the kidneys recruit basophils and activate them to produce interleukin-6 and drive T(H)17 cell responses.

Automated summary

The study reveals that fibrotic tubular cells in the kidney recruit basophils, which contribute to immune responses and kidney fibrosis. These findings are validated in both mouse models and human kidney samples, suggesting that targeting basophils might be a potential clinical strategy for managing chronic kidney disease.