Department of Biomedical Research, National Jewish Health, Denver, CO, 80206, USA.
Department of Immunology, Duke University Medical Center, Durham, NC, 27710, USA.
Mucosal Immunol. 2018 Jul;11(4):1079-1091. doi: 10.1038/s41385-018-0012-9. Epub 2018 Feb 21.
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.
2 型免疫由两个不同的 CD4+ T 细胞亚群调节。滤泡辅助性 T 细胞（Tfh）对于 2 型炎症的体液特征是必需的。辅助性 T 细胞 2（Th2）细胞在肺和肠道等外周组织中协调 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，我们研究了在诱导 2 型免疫期间，经典 Notch 激活是否可以对 Tfh 和 Th2 细胞命运产生不同的影响。这些研究表明，Tfh 细胞而不是 Th2 细胞的产生和功能依赖于 Notch 信号。虽然早期 Tfh 细胞的特异性受到经典树突状细胞上功能性 Notch 配体的影响，但树突状细胞以外的细胞、T 细胞、B 细胞和滤泡树突状细胞上的功能性 Notch 配体足以实现完全的 Tfh 细胞承诺。这些发现确定了 Notch 信号作为 Tfh 和 Th2 细胞命运之间的早期谱系决定因素。
