Patho-immunological mechanisms of vitiligo: the role of the innate and adaptive immunities and environmental stress factors

Safa Faraj, Elizabeth Helen Kemp, David John Gawkrodger, Safa Faraj, Elizabeth Helen Kemp, David John Gawkrodger

Abstract

Epidermal melanocyte loss in vitiligo, triggered by stresses ranging from trauma to emotional stress, chemical exposure or metabolite imbalance, to the unknown, can stimulate oxidative stress in pigment cells, which secrete damage-associated molecular patterns that then initiate innate immune responses. Antigen presentation to melanocytes leads to stimulation of autoreactive T-cell responses, with further targeting of pigment cells. Studies show a pathogenic basis for cellular stress, innate immune responses and adaptive immunity in vitiligo. Improved understanding of the aetiological mechanisms in vitiligo has already resulted in successful use of the Jak inhibitors in vitiligo. In this review, we outline the current understanding of the pathological mechanisms in vitiligo and locate loci to which therapeutic attack might be directed.

Keywords: Th1/Th2 cells; antibodies; autoimmunity; cytokines; cytotoxic T cells.

© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Immunology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Figures

Fig. 1
Fig. 1
Melanocytes are regularly exposed to environmental insults such as phenolic compounds can stimulate a state of melanocyte stress through interacting with tyrosinase and TYRP1, leading to production of DAMPs. DAMPs can then stimulate nearby dendritic cells through PRRs. Activated dendritic cells locally synthesize cytokines, inducing CD8+ T cell activation and recruitment to the skin. HMGB1 can activate ILCs with subsequent release of IFN-γ. In the progressive phase of vitiligo, melanocyte-reactive CD8+T cells produce interferon-gamma on encountering melanocyte antigens. These induce keratinocytes to secrete CXCL 9 and CXCL 10, resulting in additional recruitment of lymphocytes to the site through the CXCR3 receptor. CD8+ T cells, resident in vitiligo skin, are involved through the induction of IL-15, which results in the stimulation of IFN-γ, granzyme B and perforin. DAMPs; pathogens or damage-associated molecular patterns, TYRP1; tyrosinase-related protein-1, PRRs; pattern recognition receptors, HMGB1; high-mobility group protein B1, ILCs; innate lymphoid cells, IFN-γ; interferon (IFN)-γ, CXCR3; C-X-C chemokine receptor type 3, CXCL 9/10; C-X-C motif chemokine ligand 9/10, IL-15; interleukin-15.

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