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

Nat Immunol. 2022 Jun;23(6):947-959. doi: 10.1038/s41590-022-01200-7. Epub 2022 May 12.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Basophils*
  • Fibrosis
  • Humans
  • Kidney / metabolism
  • Kidney Tubules
  • Mice
  • Renal Insufficiency, Chronic* / metabolism
  • Single-Cell Analysis