# The role of JAK3 and TEC family kinases in vitiligo pathogenesis

## TL;DR

This paper reviews how JAK3 and TEC family kinases contribute to vitiligo, an autoimmune skin condition, and explores new targeted treatments.

## Contribution

The paper highlights recent advances in understanding JAK3 and TEC kinase roles in vitiligo and emerging targeted therapies.

## Key findings

- JAK/STAT and TEC family kinase signaling contribute to immune cell activation and melanocyte loss in vitiligo.
- Cytokines like IFN-γ, IL-2, and IL-15 drive immune cell recruitment and melanocyte apoptosis.
- New targeted therapies are emerging based on these pathways.

## Abstract

Vitiligo is an autoimmune disease characterized by the loss of skin pigmentation due to the loss of melanocytes. The pathogenesis of vitiligo is complex, involving multiple genetic factors, environmental triggers, oxidative stress, and autoimmunity against melanocytes. Stressed melanocytes release damage-associated molecular patterns, which trigger increased activation of antigen presenting cells, leading to maturation and activation of CD8+ T-cells that respond to auto-melanocyte-specific antigens. Once recruited to melanocytes, cytotoxic CD8+ and CD4+ T-cells produce cytokines, including primarily the type 1 cytokine IFN-γ, but also IL-2, IL-15, and type 2-related cytokines. Cytokines bind to fibroblasts, melanocytes, and keratinocytes to induce a positive feedback loop of immune cell recruitment to lesions, immune cell activation, and melanocyte apoptosis. The JAK/STAT pathway and TEC family kinase signaling play key roles in vitiligo pathogenesis through chemokine production, reduction of melanocyte adhesion, and immune cell activation and disease maintenance. This review summarizes recent key advances in understanding how these pathways impact vitiligo pathogenesis and details the emergence of new targeted therapies for the treatment of vitiligo.