Single-cell analysis identifies the interaction of altered renal tubules with basophils orchestrating kidney fibrosis
Journal
Nature immunology
Journal Volume
23
Journal Issue
6
Pages
947
Date Issued
2022-06
Author(s)
Doke, Tomohito
Abedini, Amin
Aldridge, Daniel L
Park, Jihwan
Hernandez, Christina M
Balzer, Michael S
Shrestra, Rojesh
Coppock, Gaia
Rico, Juan M Inclan
Han, Seung Yub
Kim, Junhyong
Xin, Sheng
Piliponsky, Adrian M
Angelozzi, Marco
Lefebvre, Veronique
Siracusa, Mark C
Hunter, Christopher A
Susztak, Katalin
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.
Subjects
MAST-CELLS; EXPRESSION; INFLAMMATION; RECRUITMENT; ACTIVATION; BLEOMYCIN; INJURY; TISSUE; BETA; IL-6
SDGs
Publisher
NATURE PORTFOLIO
Type
journal article