Frontiers in Immunology (Apr 2021)

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,
  • Yuan Tao,
  • Yuan Meng,
  • Jiadi Chen,
  • Xiaoming Feng,
  • Zhongchao Han,
  • Mingxia Shi,
  • Huifang Huang,
  • Mingzhe Han,
  • Erlie Jiang

DOI
https://doi.org/10.3389/fimmu.2021.629281
Journal volume & issue
Vol. 12

Abstract

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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.

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