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_H17 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.

炎症是纤维化的重要组成部分，但协调肾脏纤维化的免疫过程尚不清楚。在这里，我们将单细胞测序应用于肾纤维化小鼠模型。我们鉴定出具有促纤维化炎症表型的肾小管细胞子集，其特征在于与免疫细胞募集相关的细胞因子和趋化因子的表达。受体-配体相互作用分析和实验验证表明，促纤维化小管分泌的 CXCL1 招募 CXCR2 ⁺嗜碱性粒细胞。在小鼠中，这些嗜碱性粒细胞是白介素 6 和辅助 T 细胞 T _H 17 子集募集的重要来源。基因缺失或基于抗体的嗜碱性粒细胞消耗可减少肾纤维化。人肾单细胞大量基因表达和免疫染色验证了肾纤维化患者中嗜碱性粒细胞的功能。总的来说，这些研究确定嗜碱性粒细胞是肾纤维化发展的贡献者，并表明针对这些细胞可能是治疗慢性肾脏疾病的有用临床策略。