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

Autor: Doke T; Department of Medicine, Renal Electrolyte and Hypertension Division, University of Pennsylvania, Philadelphia, PA, USA., Abedini A; Department of Medicine, Renal Electrolyte and Hypertension Division, University of Pennsylvania, Philadelphia, PA, USA., Aldridge DL; Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, USA., Yang YW; Department of Medicine, Renal Electrolyte and Hypertension Division, University of Pennsylvania, Philadelphia, PA, USA., Park J; Department of Medicine, Renal Electrolyte and Hypertension Division, University of Pennsylvania, Philadelphia, PA, USA., Hernandez CM; Center for Immunity and Inflammation, Department of Medicine, New Jersey Medical School, Rutgers-The State University of New Jersey, Newark, NJ, USA., Balzer MS; Department of Medicine, Renal Electrolyte and Hypertension Division, University of Pennsylvania, Philadelphia, PA, USA., Shrestra R; Department of Medicine, Renal Electrolyte and Hypertension Division, University of Pennsylvania, Philadelphia, PA, USA., Coppock G; Department of Medicine, Renal Electrolyte and Hypertension Division, University of Pennsylvania, Philadelphia, PA, USA.; Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, USA., Rico JMI; Center for Immunity and Inflammation, Department of Medicine, New Jersey Medical School, Rutgers-The State University of New Jersey, Newark, NJ, USA., Han SY; Department of Biology, University of Pennsylvania, Philadelphia, PA, USA., Kim J; Department of Biology, University of Pennsylvania, Philadelphia, PA, USA., Xin S; Department of Medicine, Renal Electrolyte and Hypertension Division, University of Pennsylvania, Philadelphia, PA, USA., Piliponsky AM; Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, WA, USA., Angelozzi M; Division of Orthopaedic Surgery, Department of Surgery, The Children's Hospital of Philadelphia, Philadelphia, PA, USA., Lefebvre V; Division of Orthopaedic Surgery, Department of Surgery, The Children's Hospital of Philadelphia, Philadelphia, PA, USA., Siracusa MC; Center for Immunity and Inflammation, Department of Medicine, New Jersey Medical School, Rutgers-The State University of New Jersey, Newark, NJ, USA., Hunter CA; Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, USA., Susztak K; Department of Medicine, Renal Electrolyte and Hypertension Division, University of Pennsylvania, Philadelphia, PA, USA. ksusztak@pennmedicine.upenn.edu.
Jazyk: angličtina
Zdroj: Nature immunology [Nat Immunol] 2022 Jun; Vol. 23 (6), pp. 947-959. Date of Electronic Publication: 2022 May 12.
DOI: 10.1038/s41590-022-01200-7
Abstrakt: 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.
(© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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