Trained Immunity May Play a Role in the Pathogenesis of Vitiligo

While recent data emphasized the role of innate immunity in vitiligo, researchers hypothesize that trained immunity may play an even larger role in the disease’s pathogenesis, particularly as a continuous enhancer and trigger.

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A recent study review¹ examined the role of immunity in the formation of the disease. According to authors, the adaptive immune system already plays a known role in the process of melanocyte loss. However, a 2021 study² found the innate immune system may also play a role in its pathogenesis.

Researchers sought to determine whether vitiligo, like other autoimmune diseases, involves trained immunity—wherein innate immune cells experience increased reactivity over a longer-term basis.

According to authors of the review, Post et al, some autoimmune conditions already display signs of trained immunity playing a pathogenic role.

“It is hypothesized that trained immunity resulting in inflammasome activation could amplify the inflammatory response via inflammasome sensitization in auto inflammatory diseases, leading to an excessive and undesirable inflammatory response,” they wrote.

In the review, they found that several characteristics of vitiligo can be associated with trained immunity-related patterns, such as cytokines and chemokines, the metabolism of immune cells, epigenetic marks, and mTOR signaling. They found several studies demonstrating the involvement of innate immunity in vitiligo, ranging in publication year from as early as 1997 to as recent as 2022.

The 1997 study,³ for example, found that in patients with vitiligo, stimulated peripheral blood mononuclear cells (PBMCs) produced more IL-6 and IL-8 than control cells.

Other signs associated with innate immunity included:

• Abnormal DNA methylation of mononuclear cells in peripheral blood from patients with vitiligo
• Impaired (NAD+)-dependent deacetylase Sirtuin3 (SIRT3) activity was found in melanocytes of vitiligo patients, as compared to normal melanocytes
• Keratinocytes of vitiligo patients produce high levels of NLRP3 inflammasome and IL-1β
• Pigmented vitiligo skin cells treated with Pioglitazone, increased mRNA and protein levels of various anaerobic glycolytic enzymes
• Stressed keratinocytes from vitiligo patients release extracellular adenosine 5′-triphosphat

“The extensiveness of trained immunity in autoimmunity remains unknown. Even though there are to date no studies yet that prove a memory function of innate immune cells in vitiligo, these data provide genetic and clinical findings that support the potential involvement of trained immunity in the pathogenesis of vitiligo,” review authors wrote. “Assuming that trained immunity is involved in the pathogenesis of vitiligo, the question remains how trained immunity is induced and to what extent it contributes to T cell-mediated melanocyte destruction. Future studies focusing on metabolic and epigenetic changes in innate immune cell populations in vitiligo could help in elucidating the potential role of trained immunity in vitiligo pathogenesis.”

References

1. Post NF, Ginski G, Peters R, et al. Trained immunity in the pathogenesis of Vitiligo. Pigment Cell & Melanoma Research. Published online 2023. doi:10.1111/pcmr.13101
2. Seneschal, J., Boniface, K., D'Arino, A., & Picardo, M. (2021). An update on vitiligo pathogenesis. Pigment Cell & Melanoma Research, 34( 2), 236– 243.
3. Yu, H. S., Chang, K. L., Yu, C. L., Li, H. F., Wu, M. T., Wu, C. S., & Wu, C. S. (1997). Alterations in IL-6, IL-8, GM-CSF, TNF-a and IFN-y release by peripheral mononuclear cells in patients with active vitiligo. J Invest Dermatol, 108, 527– 529.