Locally organised and activated Fth1hi neutrophils aggravate inflammation of acute lung injury in an IL-10-dependent manner
Kun Wang, Muyun Wang, Ximing Liao, Shaoyong Gao, Jing Hua, Xiaodong Wu, Qian Guo, Wujian Xu, Jiaxing Sun, Yanan He, Qiang Li, Wei Gao
Abstract
Abstract Acute respiratory distress syndrome (ARDS) is a common respiratory critical syndrome with no effective therapeutic intervention. Neutrophils function in the overwhelming inflammatory process of acute lung injury (ALI) caused by ARDS; however, the phenotypic heterogeneity of pulmonary neutrophils in ALI/ARDS remains largely unknown. Here, using single-cell RNA sequencing, we identify two transcriptionally and functionally heterogeneous neutrophil populations (Fth1 hi Neu and Prok2 hi Neu) with distinct locations in LPS-induced ALI mouse lungs. Exposure to LPS promotes the Fth1 hi Neu subtype, with more inflammatory factors, stronger antioxidant, and decreased apoptosis under the regulation of interleukin-10. Furthermore, prolonged retention of Fth1 hi Neu within lung tissue aggravates inflammatory injury throughout the development of ALI/ARDS. Notably, ARDS patients have high ratios of Fth1 to Prok2 expression in pulmonary neutrophils, suggesting that the Fth1 hi Neu population may promote the pathological development and provide a marker of poor outcome.