Mast cells: "central regulatory hub" of neuro-endocrine-immune dysregulation in vitiligo

Mast cells (MCs), as innate immune cells residing in cutaneous tissues, serve as critical mediators in the cross-talk between the neuroendocrine and immune systems. Upon activation by internal or external stimuli, MCs synthesize, accumulate, and secrete a variety of regulatory mediators, thereby exerting multifaceted effects through their secretory capacity and regulatory functions. Vitiligo, a complex disorder with a heterogeneous etiology encompassing genetic susceptibility, oxidative stress, autoimmunity, and neurogenic components, remains incompletely understood. Current pathogenetic models based solely on neural, humoral, or immunological frameworks fail to provide a comprehensive explanation for its development. Despite the incomplete characterization of mechanisms driving MC accumulation in vitiligo lesions, therapeutic agents targeting MCs and their signaling pathways (e.g., ketotifen, imatinib) have already been clinically implemented. Notably, MCs exhibit bidirectional interactions with neural and endocrine systems: they respond to neurotransmitter and hormonal signals while simultaneously releasing bioactive substances that reciprocally modulate neural activity, endocrine balance, and local immune responses, ultimately impacting melanocyte function. Consequently, targeting MCs and their key signaling pathways(e.g., the MrgX2-PAR2 axis and chymase-TLR4 pathway) represents a promising novel approach for vitiligo management, with potential applications in controlling disease progression, preventing relapse, and advancing therapeutic development.