Environmental exposures increase the risk for severe lung disease, but specific drivers of persistent epithelial injury and immune dysfunction remain unclear. Here, we identify a feedback circuit triggered by chitin, a common component of airborne particles, that affects lung health after epithelial injury. In mice, epithelial damage disrupts lung chitinase activity, leading to environmental chitin accumulation, impaired epithelial renewal, and group 2 innate lymphoid cell (ILC2) activation. ILC2s, in turn, restore homeostasis by inducing acidic mammalian chitinase (AMCase) in regenerating epithelial cells and promoting chitin degradation, epithelial differentiation, and inflammatory resolution. Mice lacking AMCase or ILC2s fail to clear chitin and exhibit increased mortality and impaired epithelial regeneration after injury. These effects are ameliorated by chitinase replacement therapy, demonstrating that chitin degradation is crucial for recovery after various forms of lung perturbation. Thus, the ILC2-chitinase response circuit may serve as a target for alleviating persistent postinjury lung epithelial and immune dysfunction.

中文翻译：

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ILC2 几丁质酶回路恢复上皮损伤后的肺稳态


环境暴露会增加患严重肺部疾病的风险，但持续性上皮损伤和免疫功能障碍的具体驱动因素仍不清楚。在这里，我们确定了由几丁质触发的反馈回路，几丁质是空气中颗粒的一种常见成分，会影响上皮损伤后的肺部健康。在小鼠中，上皮损伤会破坏肺几丁质酶活性，导致环境几丁质积累、上皮更新受损和第 2 组先天性淋巴细胞 （ILC2） 激活。反过来，ILC2 通过在再生上皮细胞中诱导酸性哺乳动物几丁质酶 （AMCase） 并促进几丁质降解、上皮分化和炎症消退来恢复体内平衡。缺乏 AMCase 或 ILC2 的小鼠无法清除几丁质，并且在受伤后表现出死亡率增加和上皮再生受损。这些影响通过几丁质酶替代疗法得到改善，表明几丁质降解对于各种形式的肺扰动后的恢复至关重要。因此，ILC2-几丁质酶反应回路可作为缓解持续性损伤后肺上皮和免疫功能障碍的靶点。