Single-cell transcriptome analysis of the mouse lungs during the injury and recovery periods after lipopolysaccharide administration.

Objective: This study sought to investigate the cellular and molecular alterations during the injury and recovery periods of ALI and develop effective treatments for ALI.

Methods: Pulmonary histology at 1, 3, 6, and 9 days after lipopolysaccharide administration mice were assessed. An unbiased single-cell RNA sequencing was performed in alveoli tissues from injury (day 3) and recovery (day 6) mice after lipopolysaccharide administration. The roles of Fpr2 and Dpp4 in ALI were assessed.

Results: The most severe lung injury occurred on day 3, followed by recovery entirely on day 9 after lipopolysaccharide administration. The numbers of Il1a⁺ neutrophils, monocytes/macrophages, and Cd4⁺ and Cd8⁺ T cells significantly increased at day 3 after LPS administration; subsequently, the number of Il1a⁺ neutrophils greatly decreased, the numbers of monocytes/macrophages and Cd4⁺ and Cd8⁺ T cells continuously increased, and the number of resident alveolar macrophages significantly increased at day 6. The interactions between monocytes/macrophages and pneumocytes during the injury period were enhanced by the Cxcl10/Dpp4 pair, and inhibiting Dpp4 improved ALI significantly, while inhibiting Fpr2 did not.

Conclusions: Our results offer valuable insights into the cellular and molecular mechanisms underlying its progression and identify Dpp4 as an effective therapeutic target for ALI.