Replenishing Regulatory T Cells to Halt Depigmentation in Vitiligo

Abstract

Vitiligo is a cutaneous autoimmune disease, especially devastating to patients with darker skin tones because of the contrast between unaffected and lesional skin. We studied immune cells infiltrating vitiligo skin and found very few regulatory T cells (Tregs). Vitiligo was not associated with a reduced frequency or function of circulating Tregs. To manipulate Treg function, we used mouse models expressing melanocyte-reactive TCRs, following changes in pelage color. We also isolated splenocytes to measure Treg function and evaluated cutaneous Treg abundance. Even small numbers of Tregs transferred into depigmenting mice could effectively interfere with depigmentation. The same holds true for treatment with rapamycin, readily translatable for use in human patients; such treatment may be well tolerated. Because vitiligo skin is relatively devoid of cells that produce the chemokine CCL22, whereas circulating Tregs express normal levels of its receptor CCR4, we overexpressed Ccl22 in the skin of vitiligo-prone mice to assess the resulting levels of depigmentation. Markedly reduced depigmentation was accompanied by Treg infiltration to the skin. With several options available to support a healthy balance between Tregs and effector T cells, the next challenge will be to render such treatment antigen specific and avoid general immunosuppression.

Expression of Th17‐ and Treg‐specific transcription factors in vitiligo patients

“…In addition, decreased expression of FOXP3, HELIOS, and EOS in PBMCs of vitiligo patients supported our proposed mechanism of Th17 cell predominance and Treg cell downregulation. Moreover, a recent study reported very few Tregs in vitiligo skin and found chemokine CCL22 is responsible for attracting circulating Tregs . Collectively, the study supported our results, showing a lower number of Tregs in vitiligo skin.…”

Frontiers in alopecia areata pathobiology research

“…83 Transfer of Treg cells into a vitiligo mouse model or treatment with rapamycin, which is known to promote Treg cell function, markedly reduced depigmented lesions. 84 Functional impairment of Treg cells was also observed in the C3H/HeJ mouse model of AA 85 and in human patients with AA. 12,[85][86][87][88][89][90] Injections of low doses of IL-2 into the scalp skin of human patients with AA increased the number of Treg cells in the scalp skin and reportedly induced partial hair growth.…”

“…78 Treg cells are essential regulators of the immune system, and their alteration in number and function has been implicated in several inflammatory diseases. [79][80][81][82][83][84] Therefore a defect in Treg cell function has piqued the interest of investigators in the context of AA pathogenesis. 12,[85][86][87][88][89] Given that the eye is one of the major immune-privileged sites of mammals, key pointers arise from ophthalmologic research, and HF IP research might also inform human eye IP research.…”

The convergence theory for vitiligo: A reappraisal

“…Currently, Janus kinase (JAK) inhibitors that interfere with IFN‐γ signalling are in clinical trials . A tolerizing version of heat shock protein 70, Treg promoting treatment and antibodies that interfere with T‐cell recruitment are some promising new approaches that might be translated to the clinic. In the arena of therapeutics, it is important to consider that pathways may be affected in some patients and not in others, and that this can and should impact treatment choices.…”