Abstract

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.

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