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

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Doke T, Abedini A, Aldridge DL, Yang YW, Park J, Hernandez CM, Balzer MS, Shrestra R, Coppock G, Rico JMI, Han SY, Kim J, Xin S, Piliponsky AM, Angelozzi M, Lefebvre V, Siracusa MC, Hunter CA, Susztak K.Single-cell analysis identifies the interaction of altered renal tubules with basophils orchestrating kidney fibrosis. Nature immunology. 2022 Jun. 23(6):947-959. doi:10.1038/s41590-022-01200-7. PMID:35552540.

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Abstract

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 TH17 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.