Critical Role of Lkb1 in the Maintenance of Alveolar Macrophage Self-Renewal and Immune Homeostasis
Qianqian Wang, Song Chen, Tengda Li, Qiongmei Yang, Jingru Liu, Tao Yuan, Meng Yuan, Jiadi Chen, Xiaoming Feng, Zhongchao Han, Mingxia Shi, Huifang Huang, Mingzhe Han, Erlie Jiang
Abstract
Alveolar macrophages (AMs) are pivotal for maintaining lung immune homeostasis. We demonstrated that deletion of liver kinase b1 (Lkb1) in CD11c + cells led to greatly reduced AM abundance in the lung due to the impaired self-renewal of AMs but not the impeded pre-AM differentiation. Mice with Lkb1-deficient AMs exhibited deteriorated diseases during airway Staphylococcus aureus ( S . aureus ) infection and allergic inflammation, with excessive accumulation of neutrophils and more severe lung pathology. Drug-mediated AM depletion experiments in wild type mice indicated a cause for AM reduction in aggravated diseases in Lkb1 conditional knockout mice. Transcriptomic sequencing also revealed that Lkb1 inhibited proinflammatory pathways, including IL-17 signaling and neutrophil migration, which might also contribute to the protective function of Lkb1 in AMs. We thus identified Lkb1 as a pivotal regulator that maintains the self-renewal and immune function of AMs.