Targeting CTLA-4, PD-L1 and IDO to modulate immune responses in vitiligo

Abstract

For decades, an extensive debate is continued on the pathophysiology of vitiligo. Numerous hypotheses have been put forward, and many supported by well-documented arguments. Regardless of the initiating steps, most experts agree that an immune-based melanocyte destruction is responsible for the final steps leading to epidermal depigmentation. It is remarkable that currently the only therapeutic approach to counter this phenomenon consists of non-specific local and systemic immunosuppressants. Immunotherapy for melanoma reveals that targeting factors involved in peripheral tolerance are sufficient to break the natural defense mechanisms to develop skin depigmentations. Therapeutically enhancing these immune checkpoints seems therefore a promising long-term therapy for vitiligo. In this viewpoint, we propose this strategy as a promising therapeutic option for vitiligo. Several approaches are proposed with a focus on cytotoxic T-lymphocyte-associated protein 4, programmed death ligand-1 and indoleamine 2,3-dioxygenase.

Keywords: cytotoxic T-lymphocyte-associated protein 4; indoleamine 2,3-dioxygenase; peripheral tolerance; programmed death ligand-1; vitiligo.