Innate lymphoid cells (ILCs) play an important role in regulating immune responses at mucosal surfaces. The transcription factor T-bet is crucial for the function of ILC1s and NCR⁺ ILC3s and constitutive deletion of T-bet prevents the development of these subsets. Lack of T-bet in the absence of an adaptive immune system causes microbiota-dependent colitis to occur due to aberrant ILC3 responses. Thus, T-bet expression in the innate immune system has been considered to dampen pathogenic immune responses. Here, we show that T-bet plays an unexpected role in negatively regulating innate type 2 responses, in the context of an otherwise intact immune system. Selective loss of T-bet in ILCs leads to the expansion and increased activity of ILC2s, which has a functionally important impact on mucosal immunity, including enhanced protection from Trichinella spiralis infection and inflammatory colitis. Mechanistically, we show that T-bet controls the intestinal ILC pool through regulation of IL-7 receptor signalling. These data demonstrate that T-bet expression in ILCs acts as the key transcriptional checkpoint in regulating pathogenic vs. protective mucosal immune responses, which has significant implications for the understanding of the pathogenesis of inflammatory bowel diseases and intestinal infections.

中文翻译：

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T-bet 通过抑制 2 型先天淋巴样细胞功能来控制肠粘膜免疫反应。

先天性淋巴样细胞 (ILC) 在调节粘膜表面的免疫反应中起着重要作用。^{转录因子 T-bet 对 ILC1s 和 NCR +}的功能至关重要ILC3 和 T-bet 的组成型缺失阻止了这些子集的发展。在没有适应性免疫系统的情况下缺乏 T-bet 会导致由于异常的 ILC3 反应而发生微生物群依赖性结肠炎。因此，先天免疫系统中的 T-bet 表达被认为可以抑制致病性免疫反应。在这里，我们表明，在免疫系统完好无损的情况下，T-bet 在负调节先天 2 型反应方面发挥了意想不到的作用。ILC 中 T-bet 的选择性缺失导致 ILC2 的扩增和活性增加，这对粘膜免疫具有重要的功能影响，包括增强对旋毛虫感染和炎症性结肠炎的保护作用。从机制上讲，我们表明 T-bet 通过调节 IL-7 受体信号传导来控制肠道 ILC 池。