Single-cell profiling identifies mechanisms of inflammatory heterogeneity in chronic rhinosinusitis

Weiqing Wang # 1, Yi Xu # 2, Lun Wang # 3, Zhenzhen Zhu 1, Surita Aodeng 1, Hui Chen 2, Menghua Cai 2, Zhihao Huang 4, Jinbo Han 1, Lei Wang 1, Yuxi Lin 1, Yu Hu 2, Liangrui Zhou 5, Xiaowei Wang 1, Yang Zha 1, Weihong Jiang 6, Zhiqiang Gao 1, Wei He 7, Wei Lv 8, Jianmin Zhang 9 10

 

Nat Immunol. 2022 Oct;23(10):1484-1494. doi: 10.1038/s41590-022-01312-0. Epub 2022 Sep 22.

PMID: 36138182

 

Abstract

The heterogeneous cellular microenvironment of human airway chronic inflammatory diseases, including chronic rhinosinusitis (CRS) and asthma, is still poorly understood. Here, we performed single-cell RNA sequencing (scRNA-seq) on the nasal mucosa of healthy individuals and patients with three subtypes of CRS and identified disease-specific cell subsets and molecules that specifically contribute to the pathogenesis of CRS subtypes. As such, ALOX15+ macrophages contributed to the type 2 immunity-driven pathogenesis of one subtype of CRS, eosinophilic CRS with nasal polyps (eCRSwNP), by secreting chemokines that recruited eosinophils, monocytes and T helper 2 (TH2) cells. An inhibitor of ALOX15 reduced the release of proinflammatory chemokines in human macrophages and inhibited the overactivation of type 2 immunity in a mouse model of eosinophilic rhinosinusitis. Our findings advance the understanding of the heterogeneous immune microenvironment and the pathogenesis of CRS subtypes and identify potential therapeutic approaches for the treatment of CRS and potentially other type 2 immunity-mediated diseases.