Modified Long-Lasting Immunity may Play a Role in Vitiligo

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Highlights:

• Vitiligo is an autoimmune disease against skin cells, leading to milky-white skin patches
• While the role of the adaptive immune system in vitiligo has been described extensively
• More recent data emphasized the involvement of the innate immune system in the vitiligo disease process

Vitiligo is an autoimmune disease in which skin cells are destroyed by immune cells resulting in depigmented skin patches. While adaptive immunity plays a clear role in disease progression, initiating factors are largely unknown. In recent research, the innate immune system seems to play a role in the initiation of this disease process.

The prevalence of vitiligo ranges from 0.06 to 2.28% throughout the world, whereas this was 0.0-2.16% in children/adolescents. Skin cells of vitiligo patients have an increased sensitivity to endogenous or external stress factors, such as trauma or ultraviolet radiation, which increase the production of damage-associated oxidative stress (1^✔).

‘Trained immunity in which the Innate immune system shows an enhanced response to a secondary trigger such as vaccination, might be involved in vitiligo. #vitiligo #InnateImmunity #AutoimmuneDisease #TrainedImmunity’

Although more knowledge has been acquired about the role of the innate immune system in the pathogenesis of vitiligo, the question remains why vitiligo patients' immune response becomes overly activated.

Trained Immunity and Vitiligo: How are they Connected?

Previously, it was believed that only the adaptive immune system could develop immunological memory. However, this view has been challenged when the innate immune system previously exposed to certain stimuli showed an enhanced immunological response to a secondary trigger, indicating a memory function of the innate immune system. This concept is called trained immunity (2^✔).

In contrast to adaptive memory, trained immunity is regulated by genetic changes. Thus, although less specific than the classic adaptive immune memory, trained immunity results in an improved immune response upon second exposure.

Although trained immunity is a beneficial immune response, there are indications of a pathogenic role in autoimmune diseases. It is hypothesized that trained immunity could lead to an excessive and undesirable inflammatory response.

Various published studies on innate immune cells obtained from vitiligo patients provide the cellular evidence supporting innate immune involvement. It was found that vitiligo patients produced more IL-8 and IL-6 than healthy controls upon stimulation.

Furthermore, indications for trained immunity involvement were found based on changes in innate immune cells. Blood cells obtained from vitiligo patients expressed increased expression of the TCA cycle enzyme malate dehydrogenase and showed different gene expression patterns, compared to healthy donors.

The extensiveness of trained immunity remains unknown. To date, there have been no studies that definitively prove the existence of a memory function in 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.

Assuming that trained immunity is involved in the pathogenesis of vitiligo, the question of how much-trained immunity is induced and to what extent it contributes to skin cell destruction remains (3^✔).

Future studies focusing on metabolic and genetic changes in innate cell populations in vitiligo should be initiated to understand the role of this process in this important disease. Such a study not only helps in elucidating the role of trained immunity in vitiligo but also decipher whether trained immunity could be a new therapeutic target in vitiligo.

References:

1. Trained immunity in the pathogenesis of vitiligo - (https:onlinelibrary.wiley.com/doi/10.1111/pcmr.13101)
2. Immunometabolic Pathways in BCG-Induced Trained Immunity - (https:www.cell.com/cell-reports/fulltext/S2211-1247(16)31552-2)
3. Defining trained immunity and its role in health and disease - (https:www.nature.com/articles/s41577-020-0285-6)

Source: Medindia

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