Understanding autoimmunity of vitiligo and alopecia areata

Abstract

Purpose of review Vitiligo and alopecia areata are common, disfiguring skin diseases. Treatment options are limited and include non-targeted approaches such as corticosteroids, topical calcineurin inhibitors, narrow band UVB phototherapy, and other immune-modifying agents. The purpose of this article is to review shared, novel mechanisms between vitiligo and alopecia areata, as well as discuss how they inform the development of future targeted treatments. Recent findings Vitiligo and alopecia areata are both autoimmune diseases, and striking similarities in pathogenesis have been identified at the level of both the innate and adaptive immune system. Increased reactive oxygen species and high cellular stress level have been suggested as the initiating trigger of the innate immune system in both diseases, and genome-wide association studies have implicated risk alleles that influence both innate and adaptive immunity. Most importantly, mechanistic studies in mouse models of vitiligo and alopecia areata have specifically implicated an IFN-γ-driven immune response, including IFN-γ, IFN-γ-induced chemokines, and cytotoxic CD8+ T cells as the main drivers of disease pathogenesis. These recent discoveries may reveal an effective strategy to develop new treatments, and several proof-of-concept clinical studies support this hypothesis. Summary The identification of IFN-γ-driven immune signaling pathways has enabled discoveries of potential new treatments for vitiligo and alopecia areata, and supports initiation of larger clinical trials.

Vitiligo Pathogenesis and Emerging Treatments

“…Cytokines secreted within the skin act as an early signal to help these autoreactive T cells locate stressed melanocytes. This is probably important because the epidermis is not vascularized, and so active mechanisms are required to help them efficiently locate melanocytes (33). Chemokines are small, secreted proteins that act as chemoattractants to guide T cell migration.…”

Expression analysis of PD‐1 and Tim‐3 immune checkpoint receptors in patients with vitiligo; positive association with disease activity

“…Various factors are involved in the pathogenesis of vitiligo including genetics, environment, oxidative stress as well as innate and acquired immunity . Oxidative stress triggers chemokines production from keratinocytes causing infiltration of melanocyte antigen‐specific CD8 + T cells into the epidermis, which have an adverse effect on the morphology of melanocytes and also induce their apoptosis by direct killing and IFN‐γ secretion . Several regulatory mechanisms including the concentration of indoleamine 2, 3‐dioxygenase, expression of programmed cell death protein ligand‐1 (PD‐L1) and cytotoxic T lymphocyte‐associated protein‐4 (CTLA‐4) by melanocytes, and also presence of Foxp3 + regulatory T cells have been introduced for peripheral tolerance induction and inhibition of autoimmune responses in the skin.…”

Alopecia areata and overt thyroid diseases: A nationwide population‐based study

“…Although the etiopathogenesis of AA has not been completely established yet, an autoimmune nature of the disease has been suspected with genetic predisposition . The hair follicle is an inherently immune‐privileged site with low expression levels of major histocompatibility complex . It is assumed that AA results from a breakdown in immune privilege and subsequent assault on the follicle by CD8 + T lymphocytes .…”

“…5 The hair follicle is an inherently immune-privileged site with low expression levels of major histocompatibility complex. 6 It is assumed that AA results from a breakdown in immune privilege and subsequent assault on the follicle by CD8 + T lymphocytes. 7 A recent study conclusively revealed a key role of a specific cytotoxic T-cell subset, NKG2D + CD + cytotoxic T cells, in the infiltration and destruction of the upper part of the hair bulb, without harming regenerative stem cells.…”