SPHK2-Generated S1P in CD11b⁺ Macrophages Blocks STING to Suppress the Inflammatory Function of Alveolar Macrophages.

ABSTRACT: Acute lung injury (ALI) is a lethal inflammatory lung disorder whose incidence is on the rise. Alveolar macrophages normally act to resolve inflammation, but when dysregulated they can provoke ALI. We demonstrate that monocyte-derived macrophages (CD11b⁺ macrophages) recruited into the airspace upregulate the anti-inflammatory function of alveolar macrophages by suppressing their stimulator of type 1 interferon gene (STING) signaling. Depletion of CD11b⁺ macrophages in mice (macrophage^dep mice) after endotoxin or after Pseudomonas aeruginosa causes expansion of the inflammatory alveolar macrophage population, leading to neutrophil accumulation, irreversible loss of lung vascular barrier function, and lethality. We show that CD11b⁺ macrophages sup

SUBMITTER: Joshi JC 

PROVIDER: S-EPMC7170050 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature