By enhancing tissue repair and modulating immune responses, Foxp3⁺ regulatory T cells (Tregs) play essential roles in resolution from lung injury. The current study investigated the effects that Tregs exert directly or indirectly on the transcriptional profiles of type 2 alveolar epithelial (AT2) cells during resolution in an experimental model of acute lung injury. Purified AT2 cells were isolated from uninjured mice or mice recovering from LPS-induced lung injury, either in the presence of Tregs or in Treg-depleted mice, and transcriptome profiling identified differentially expressed genes. Depletion of Tregs resulted in altered expression of 49 genes within AT2 cells during resolution, suggesting that Tregs present in this microenvironment influence AT2-cell function. Biological processes from Gene Ontology enriched in the absence of Tregs included those describing responses to IFN. Neutralizing IFN-γ in Treg-depleted mice reversed the effect of Treg depletion on inflammatory macrophages and B cells by preventing the increase in inflammatory macrophages and the decrease in B cells. Our results provide insight into the effects of Tregs on AT2 cells. Tregs directly or indirectly impact many AT2-cell functions, including IFN type I and II–mediated signaling pathways. Inhibition of IFN-γ expression and/or function may be one mechanism through which Tregs accelerate resolution after acute lung injury.

通过增强组织修复和调节免疫反应，Foxp3 ⁺调节性 T 细胞 (Tregs) 在肺损伤的解决中发挥重要作用。目前的研究调查了在急性肺损伤实验模型中，Tregs 在消退期间直接或间接对 2 型肺泡上皮 (AT2) 细胞转录谱的影响。纯化的 AT2 细胞是从未受伤的小鼠或从 LPS 诱导的肺损伤中恢复的小鼠中分离出来的，无论是在 Treg 存在的情况下还是在 Treg 耗尽的小鼠中，转录组分析确定了差异表达的基因。在解析过程中，Treg 的消耗导致 AT2 细胞内 49 个基因的表达发生改变，这表明该微环境中存在的 Treg 会影响 AT2 细胞的功能。在缺乏 Tregs 的情况下，来自 Gene Ontology 的生物过程包括描述对 IFN 的反应的生物过程。在 Treg 耗尽的小鼠中中和 IFN-γ 通过阻止炎性巨噬细胞的增加和 B 细胞的减少，逆转了 Treg 耗尽对炎性巨噬细胞和 B 细胞的影响。我们的结果提供了对 Tregs 对 AT2 细胞影响的洞察。Tregs 直接或间接影响许多 AT2 细胞功能，包括 I 型和 II 型干扰素介导的信号通路。抑制 IFN-γ 表达和/或功能可能是 Tregs 在急性肺损伤后加速消退的一种机制。包括干扰素 I 型和 II 型介导的信号通路。抑制 IFN-γ 表达和/或功能可能是 Tregs 在急性肺损伤后加速消退的一种机制。包括 I 型和 II 型干扰素介导的信号通路。抑制 IFN-γ 表达和/或功能可能是 Tregs 在急性肺损伤后加速消退的一种机制。