CD4⁺ T cells are critical in orchestrating immune responses against various pathogens and cancer but can also be drivers of autoimmune disease, allergy and pro-tumour responses. Naïve CD4⁺ T cells polarise into specialised T helper cell subsets with unique effector functions. While the guiding transcription factors and effector molecules of the T helper cell lineages are well understood, the signalling pathways orchestrating the intricate T helper cell polarisation programmes remain poorly understood. Here we review an emerging role of Hedgehog signalling – a classical morphogen signalling pathway – in T helper cell polarisation. Importantly, the Hedgehog pathway is pharmacologically highly tractable and existing clinically-approved Hedgehog inhibitors may prove useful therapeutic modulators of T helper cell-driven immune responses.

CD4 ⁺ T 细胞对于协调针对各种病原体和癌症的免疫反应至关重要，但也可能是自身免疫性疾病、过敏和促肿瘤反应的驱动因素。初始 CD4 ⁺ T 细胞极化为具有独特效应功能的专门 T 辅助细胞亚群。虽然 T 辅助细胞谱系的指导转录因子和效应分子已被充分了解，但协调复杂的 T 辅助细胞极化程序的信号传导途径仍然知之甚少。在这里，我们回顾了 Hedgehog 信号传导（一种经典的形态发生素信号传导途径）在 T 辅助细胞极化中的新兴作用。重要的是，Hedgehog 通路在药理学上非常容易处理，现有临床批准的 Hedgehog 抑制剂可能被证明是 T 辅助细胞驱动的免疫反应的有用治疗调节剂。