JAK inhibitors in immune regulation and treatment of vitiligo

Abstract

Vitiligo, a disorder marked by hypopigmentation, significantly impacts patients' quality of life and mental health. This condition results from the reduction or dysfunction of melanocytes, which are crucial for skin and hair pigmentation. Current treatments include glucocorticoids, immunosuppressants, phototherapy, vitamin D3 analogues, and surgical interventions. Recent research has revealed that hyperactivation of Janus kinase (JAK) and its downstream signaling pathways intensifies cytotoxic T cell activity and weakens melanocytes' defense against environmental stressors. Additionally, the aberrant expression of pro-inflammatory cytokines such as Interferon-gamma (IFN-γ) and Tumor Necrosis Factor-alpha (TNF-α) plays a critical role in the pathogenesis of vitiligo by disrupting melanocyte function and promoting immune-mediated destruction. Clinical trials and basic research have demonstrated the efficacy of JAK inhibitors in modulating these cytokine pathways and promoting melanocyte repigmentation. This review provides a comprehensive analysis of JAK inhibitors, exploring their mechanisms and latest applications in regulating cytokine and skin immune responses, aiming to optimize their use in vitiligo therapy.

Keywords: Biomarkers; Cytokines; Immune regulation; Janus kinase inhibitors; Skin pigmentation; Vitiligo.