The OX40-OX40L Co-stimulatory pathway in dermatology: emerging frontiers for therapeutic approaches

The OX40/OX40L co-stimulatory signaling pathway plays a crucial role in T cell activation, differentiation, expansion, and survival across various human tissues, including the skin and mucosal surfaces. Alterations in this pathway have been implicated in diverse immune-mediated skin conditions such as tumor microenvironments; atopic dermatitis, characterized by type 2 inflammation; psoriasis and hidradenitis suppurativa, associated with Th17 responses; vitiligo, involving dysregulated interferon-producing CD8⁺ T cells. The complex interplay between mast cells expressing OX40L and T cells expressing OX40, which in some contexts can inhibit regulatory T cell (Treg) function and promote Th17 differentiation, underscores the therapeutic potential of either antagonizing or agonizing this co-stimulatory pathway. In this review, we discuss selected dermatological diseases in which the OX40/OX40L axis appears relevant to their immunopathogenesis and may serve as a potential therapeutic target.