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=Volume 12 - 2021

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=Alveolar macrophages (AMs) are pivotal for maintaining lung immune homeostasis. We demonstrated that deletion of liver kinase b1 (Lkb1) in CD11c+ cells led to the greatly reduced AMs abundance in lung due to the impaired self-renewal of AMs, but not the impeded pre-AMs differentiation. Mice with Lkb1-deficient AMs had deteriorated diseases during airway Staphylococcus. aureus (S. aureus) infection and allergic inflammation, with the excessive accumulation of neutrophils and severer pathology in lung. The drug-mediated AM-depletion experiments in wild-type mice indicated a causative reason of AMs reduction in aggravated diseases in Lkb1 conditional knockout mice. Transcriptomic sequencing also revealed that Lkb1 inhibited the pro-inflammatory pathways including IL-17 signaling and neutrophils migration, which might also contribute to the protective function of Lkb1 in AMs. We thus identified Lkb1 as a pivotal regulator to maintain self-renewal and immune function of AMs.