Type-2 immunity is regulated by two distinct CD4+ T-cell subsets. T follicular helper (Tfh) cells are required for humoral hallmarks of type-2 inflammation. T-helper type-2 (Th2) cells orchestrate type-2 inflammation in peripheral tissues, such as the lung and intestine. Given the importance of Notch signaling in the establishment of other CD4+ T-helper cell subsets, we investigated whether canonical Notch activation could differentially impact Tfh and Th2 cell fate during the induction of type-2 immunity. These studies show that Tfh cell, but not Th2 cell, generation and function is reliant on Notch signaling. While early Tfh cell specification is influenced by functional Notch ligands on classical dendritic cells, functional Notch ligands on cells other than dendritic cells, T cells, B cells, and follicular dendritic cells are sufficient to achieve full Tfh cell commitment. These findings identify Notch signaling as an early lineage-determining factor between Tfh and Th2 cell fate.

中文翻译：

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Notch 信号代表滤泡 T 辅助细胞和典型 T 辅助细胞 2 细胞命运之间的重要检查点。

2 型免疫受两个不同的 CD4+ T 细胞亚群调节。T 滤泡辅助 (Tfh) 细胞是 2 型炎症的体液标志所必需的。T 辅助 2 型 (Th2) 细胞在肺和肠等外周组织中协调 2 型炎症。鉴于 Notch 信号在其他 CD4+ T 辅助细胞亚群的建立中的重要性，我们研究了典型的 Notch 激活是否会在诱导 2 型免疫期间对 Tfh 和 Th2 细胞命运产生不同影响。这些研究表明，Tfh 细胞而非 Th2 细胞的生成和功能依赖于 Notch 信号传导。虽然早期 Tfh 细胞规格受经典树突细胞上功能性 Notch 配体的影响，但树突细胞、T 细胞、B 细胞以外的细胞上的功能性 Notch 配体，和滤泡树突状细胞足以实现完整的 Tfh 细胞定型。这些发现将 Notch 信号识别为 Tfh 和 Th2 细胞命运之间的早期谱系决定因素。