Hedgehog signalling in CD4⁺ T helper cell polarisation

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.