Department of Dermatology, Netherlands Institute for Pigment Disorders, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam Institute for Infection and Immunity, Amsterdam, Netherlands.
Department of Dermatology, Netherlands Institute for Pigment Disorders, Amsterdam University Medical Centers, VU University, Amsterdam Institute for Infection and Immunity, Amsterdam, The Netherlands.
Pigment Cell Melanoma Res. 2023 Sep;36(5):348-354. doi: 10.1111/pcmr.13101. Epub 2023 Jun 9.
Vitiligo is caused by an autoimmune reaction against melanocytes leading to melanocyte loss. The cause of vitiligo is an interaction between genetic susceptibility and environmental factors. Both the adaptive immune system-through cytotoxic CD8+ T cells and melanocyte specific antibodies-and the innate immune system are involved in these immune processes in vitiligo. While recent data stressed the importance of innate immunity in vitiligo, the question remains why vitiligo patients' immune response becomes overly activated. Could a long-term increase in innate memory function, described as trained immunity after vaccination and in other inflammatory diseases, play a role as an enhancer and continuous trigger in the pathogenesis of vitiligo? After exposure to certain stimuli, innate immune system is able to show an enhanced immunological response to a secondary trigger, indicating a memory function of the innate immune system, a concept termed trained immunity. Trained immunity is regulated by epigenetic reprogramming, including histone chemical modifications and changes in chromatin accessibility that cause sustained changes in the transcription of specific genes. In responses to an infection, trained immunity is beneficial. However, there are indications of a pathogenic role of trained immunity in inflammatory and autoimmune diseases, with monocytes presenting features of a trained phenotype, resulting in increased cytokine production, altered cell metabolism through mTOR signaling, and epigenetic modifications. This hypothesis paper focusses on vitiligo studies that have shown these indications, suggesting the involvement of trained immunity in vitiligo. 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.
白癜风是由针对黑素细胞的自身免疫反应引起的，导致黑素细胞丧失。白癜风的病因是遗传易感性和环境因素之间的相互作用。适应性免疫系统——通过细胞毒性 CD8+T 细胞和黑素细胞特异性抗体——以及固有免疫系统都参与了白癜风中的这些免疫过程。虽然最近的数据强调了固有免疫在白癜风中的重要性，但问题仍然是为什么白癜风患者的免疫反应会过度激活。在接种疫苗和其他炎症性疾病后被描述为训练有素的免疫的固有记忆功能的长期增加，是否可以作为白癜风发病机制中的增强剂和持续触发因素发挥作用？固有免疫系统在暴露于某些刺激后能够对二次触发表现出增强的免疫反应，表明固有免疫系统具有记忆功能，这一概念称为训练有素的免疫。训练有素的免疫受表观遗传重编程调控，包括组蛋白化学修饰和染色质可及性的变化，导致特定基因转录的持续变化。在感染反应中，训练有素的免疫是有益的。然而，有迹象表明训练有素的免疫在炎症性和自身免疫性疾病中具有致病作用，其中单核细胞呈现出训练表型的特征，导致细胞因子产生增加、通过 mTOR 信号改变细胞代谢以及表观遗传修饰。这篇假设性论文重点关注了已经表明这些迹象的白癜风研究，表明训练有素的免疫参与了白癜风。未来专注于白癜风固有免疫细胞群体代谢和表观遗传变化的研究可能有助于阐明训练有素的免疫在白癜风发病机制中的潜在作用。
