CNS1依赖性调节性T细胞从急性肺损伤中恢复

摘要(中文译文)

调节性T细胞（Tregs）在介导急性肺损伤（ALI）的恢复中起着至关重要的作用。然而，在急性炎症消退过程中，肺中功能异质性Treg亚群的复杂作用尚不清楚。为了研究外周诱导的Treg的作用，我们利用了缺乏Foxp3基因座保守非编码序列1（CNS1）的小鼠，这是一种损害外周Treg诱导的遗传缺失。我们发现CNS1缺陷小鼠在ALI期间表现出更高的死亡率和延迟的消退。在流感期间，通过CNS1诱导的Tregs调节了肺部的抗病毒和促炎免疫反应。从机制上讲，单细胞RNA测序表明，CNS1缺陷的Treg未能完全参与支持肺部最佳抑制和修复功能的Treg转录程序。我们的研究结果强调了CNS1依赖性外周诱导的Treg在决定ALI严重程度方面的关键作用，为如何治疗性地利用不同的Treg亚群来减轻呼吸系统疾病期间的组织损伤提供了见解。

Abstract

Regulatory T cells (Tregs) play a crucial role in mediating recovery from acute lung injury (ALI). However, the complex roles of functionally heterogeneous Treg subsets in the lung during the resolution of acute inflammation remain unclear. To investigate the role of peripherally induced Tregs, we utilized mice lacking conserved noncoding sequence 1 (CNS1) of the Foxp3 locus, a genetic deletion that impairs peripheral Treg induction. We found that CNS1-deficient mice exhibit greater mortality and delayed resolution during ALI. Tregs induced via CNS1 modulated antiviral and proinflammatory immune responses in the lung during influenza. Mechanistically, single-cell RNA sequencing reveals that CNS1-deficient Tregs fail to fully engage the Treg transcriptional program that supports optimal suppressive and reparative function in the lung. Our findings highlight a critical role for CNS1-dependent peripherally induced Tregs in determining ALI severity, providing insight into how distinct Treg subpopulations may be therapeutically harnessed to mitigate tissue damage during respiratory disease.

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