γδ T Cells and the Extracellular Matrix: From Established Adhesion to an Unmapped Mechanotransduction Pathway in Barrier Immunity, Neuroinflammation and Cancer

γδ T cells are disproportionately enriched in the ECM-rich barrier tissues of the gut and skin, and are already known to adhere to the extracellular matrix (ECM) through a broad integrin repertoire, including CD103, CD49a and the wider β1, β2 and β7 integrin families. In conventional αβ T cells, this kind of integrin-ECM engagement has been shown to drive a defined intracellular mechanotransduction pathway: actin polymerisation, nuclear deformation and YAP translocation that together promote IL-2-dependent activation, independently of the T cell receptor. Whether the same pathway operates in γδ T cells has never been tested, even as recent work shows that γδ T cells respond functionally to matrix viscoelasticity. This review brings together the descriptive literature on γδ T cell behaviour at barrier tissues with the mechanistic mechanotransduction literature built in αβ T cells, to argue that the molecular link between the two, rather than ECM engagement in general, is the genuine and clinically relevant gap. It distinguishes this ECM-mechanosensing question from TCR mechanosensing, considers a possible bidirectional feedback loop between γδ T cells and the matrix they occupy, and develops testable, disease-specific hypotheses in inflammatory bowel disease, chronic wound healing, traumatic brain injury and multiple sclerosis, and solid tumour immunotherapy, each linked to an existing drug or clinical precedent.