AUTHOR=Wang Qianqian , Chen Song , Li Tengda , Yang Qiongmei , Liu Jingru , Tao Yuan , Meng Yuan , Chen Jiadi , Feng Xiaoming , Han Zhongchao , Shi Mingxia , Huang Huifang , Han Mingzhe , Jiang Erlie 

TITLE=Critical Role of Lkb1 in the Maintenance of Alveolar Macrophage Self-Renewal and Immune Homeostasis

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.629281

DOI=10.3389/fimmu.2021.629281

ISSN=1664-3224

ABSTRACT=<p>Alveolar macrophages (AMs) are pivotal for maintaining lung immune homeostasis. We demonstrated that deletion of liver kinase b1 (Lkb1) in CD11c<sup>+</sup> 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 <italic>Staphylococcus aureus</italic> (<italic>S</italic>. <italic>aureus</italic>) 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.</p>