Is targeting circulating T blood cells a therapeutic option for vitiligo?

Vitiligo is an autoimmune depigmenting skin disorder that results from the loss of melanocytes due to an altered proportion and/or function of effector and regulatory T cells.1, 2 More specifically, the T‐helper/cytotoxic T‐cell (Th)1/(Tc)1 immune response is affected by an increased production of interferon (IFN)‐γ and tumour necrosis factor (TNF)‐α.

In this issue of the BJD, Martins et al. reaffirm the role of Th1 and Tc1 cell subsets in vitiligo disease and its production of both IFN‐γ and TNF‐α.3 Furthermore, their results show that the frequency of CD4+ and CD8+ circulating Th17/Tc17, Th1/Th17 and Tc1/Tc17 effector memory T‐cell subsets is significantly lower in patients with vitiligo (both with stable and active disease) and psoriasis, in comparison with healthy donors. These findings suggest a possible migration of distinct T‐cell subsets from the blood into the skin. The same authors have previously shown that vitiligo perilesional skin is imprinted with pathogenic CD8+ resident memory T cells (TRM).4 Future studies should investigate which blood memory T‐cell subsets ultimately differentiate into vitiligo‐pathogenic TRM cells.

Many studies on patients with vitiligo focus exclusively on patients with active disease. However, Martins et al.3 show that the same immune response is found in the blood of patients with active and stable disease. Previous studies have shown the presence of TRM cells in vitiligo skin,4, 5, 6 which are likely involved during flares, as previously shown in psoriasis.7

The precise role of circulatory Th1/Th17, Tc1/Tc17 and Th17 cells and the production of interleukin (IL)‐17 in patients with vitiligo remains unclear. Studies have shown increased IL‐17 expression both in blood and perilesional skin of patients with vitiligo,8 and serum level of IL‐17 correlated with disease activity,9 while other studies have observed a similar frequency of IL‐17‐producing CD4 and CD8 T cells in vitiligo skin and skin from unaffected individuals.4 A single‐arm pilot study using secukinumab showed that directly targeting the IL‐17 pathway is not a reliable strategy in vitiligo.10 The work of Martins et al.3 raises important questions, such as whether pathogenic IFN‐γ‐producing cells also secrete IL‐17 in patients with vitiligo or whether the IL‐17 production is a consequence of the activation of Th1/Th17 or Tc1/Tc17 cells.

Together, these findings indicate that targeting blood‐specific T‐cell subsets that migrate into the skin of patients with vitiligo could prevent the flare of the disease. Nevertheless, further studies will have to elucidate which circulating skin‐homing T‐cell subsets truly cause the cutaneous changes seen in patients with vitiligo.