State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
Department of Hematology, The First Affiliated Hospital of Kunming Medical University, Hematology Research Center of Yunnan Province, Kunming, China.
Front Immunol. 2021 Apr 22;12:629281. doi: 10.3389/fimmu.2021.629281. eCollection 2021.
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 (. ) 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.
肺泡巨噬细胞 (AMs) 对于维持肺部免疫稳态至关重要。我们发现，由于 AMs 的自我更新受损而不是前 AM 分化受阻，导致 Lkb1 敲除 CD11c 细胞后肺部 AM 的丰度大大降低。缺乏 Lkb1 的 AM 的小鼠在气道感染和过敏性炎症期间表现出疾病恶化，中性粒细胞过度积累和更严重的肺部病理学。野生型小鼠的 AM 耗竭药物实验表明，Lkb1 条件性敲除小鼠加重疾病中 AM 减少的原因。转录组测序还揭示 Lkb1 抑制了促炎途径，包括 IL-17 信号和中性粒细胞迁移，这也可能有助于 Lkb1 在 AMs 中的保护功能。因此，我们确定 Lkb1 是维持 AM 自我更新和免疫功能的关键调节因子。
