|
|
白癜风细胞免疫学发病机制的研究进展
|
Abstract:
白癜风是一种获得性免疫介导的色素沉着性疾病，临床特征是皮肤上出现界限清楚的色素脱失。目前的研究结果强调了免疫细胞及其介质在白癜风免疫发病机制中的关键作用。氧化应激介导的先天免疫细胞(如树突状细胞、自然杀伤细胞和ILC-1细胞)的激活被认为是白癜风早期发病的关键事件。先天免疫细胞充当适应性免疫细胞的桥梁，包括T辅助细胞1细胞、细胞毒性T细胞和常驻记忆T细胞。IFN-γ是激活JAK/STAT通路的主要细胞因子介质，导致角质形成细胞产生关键趋化因子CXCL9和CXCL10。免疫细胞和非免疫细胞之间复杂的相互作用最终导致黑素细胞凋亡。本文总结了目前关于导致白癜风的免疫发病机制以及该疾病炎症途径中的关键细胞和细胞因子。
Vitiligo is an acquired immune-mediated pigmentation disorder characterized by well-defined depigmentation on the skin. The current research findings emphasize the crucial role of immune cells and their mediators in the immune pathogenesis of vitiligo. The activation of innate immune cells (such as dendritic cells, natural killer cells, and ILC-1 cells) mediated by oxidative stress is considered a key event in the early onset of vitiligo. Congenital immune cells act as a bridge for adaptive immune cells, including T helper cell-1 cells, cytotoxic T cells, and resident memory T cells. IFN-γ is the main cytokine mediator that activates the JAK/STAT pathway, leading to the production of key chemokines CXCL9 and CXCL10 by keratinocytes. The complex interactions between immune cells and non immune cells ultimately lead to melanocyte apoptosis. This article summarizes the current immune pathogenesis of vitiligo and the key cells and cytokines involved in the inflammatory pathway of the disease.
| [1] | Abdel-Malek, Z., Jordan, C., Ho, T., et al. (2020) The Enigma and Challenges of Vitiligo Pathophysiology and Treatment. Pigment Cell & Melanoma Research, 33, 778-787. https://doi.org/10.1111/pcmr.12878 |
| [2] | Bergqvist, C. and Ezzedine, K. (2020) Vitiligo: A Review. Dermatology, 236, 571-592. https://doi.org/10.1159/000506103 |
| [3] | Bergqvist, C. and Ezzedine, K. (2021) Vitiligo: A Focus on Pathogenesis and Its Therapeutic Implications. The Journal of Dermatology, 48, 252-270. https://doi.org/10.1111/1346-8138.15743 |
| [4] | Boniface, K. and Seneschal, J. (2019) Vitiligo as a Skin Memory Disease: The Need for Early Intervention with Immunomodulating Agents and a Maintenance Therapy to Target Resident Memory T Cells. Experimental Dermatology, 28, 656-661. https://doi.org/10.1111/exd.13879 |
| [5] | Chaudhary, A., Patel, M. and Singh, S. (2022) Current Debates on Etiopathogenesis and Treatment Strategies for Vitiligo. Current Drug Targets, 23, 1219-1238. https://doi.org/10.2174/1389450123666220406125645 |
| [6] | Cheuk, S., Schlums, H., Gallais Serezal, I., et al. (2017) CD49a Expression Defines Tissue-Resident CD8( ) T Cells Poised for Cytotoxic Function in Human Skin. Immunity, 46, 287-300. https://doi.org/10.1016/j.immuni.2017.01.009 |
| [7] | Dwivedi, M., Laddha, N., Arora, P., et al. (2013) Decreased Regulatory T-Cells and CD4( )/CD8( ) Ratio Correlate with Disease Onset and Progression in Patients with Generalized Vitiligo. Pigment Cell & Melanoma Research, 26, 586-591. https://doi.org/10.1111/pcmr.12105 |
| [8] | Gholijani, N., Yazdani, M. and Dastgheib, L. (2020) Predominant Role of Innate Pro-Inflammatory Cytokines in Vitiligo Disease. Archives of Dermatological Research, 312, 123-131. https://doi.org/10.1007/s00403-019-01996-9 |
| [9] | Hojman, L., Cabrera, R., Karsulovic, C., et al. (2021) The Role of CXCL10 and IL-18 as Markers of Repigmentation Response in Nonsegmental Vitiligo Treated with Narrowband UVB Phototherapy: A Prospective Cohort Study. Journal of Investigative Dermatology, 141, 1833-1836.E1. https://doi.org/10.1016/j.jid.2020.12.021 |
| [10] | Howell, M.D., Kuo, F.I. and Smith, P.A. (2019) Targeting the Janus Kinase Family in Autoimmune Skin Diseases. Frontiers in Immunology, 10, Article No. 2342. https://doi.org/10.3389/fimmu.2019.02342 |
| [11] | Kumar Jha, A., Sonthalia, S., Lallas, A., et al. (2018) Dermoscopy in Vitiligo: Diagnosis and Beyond. International Journal of Dermatology, 57, 50-54. https://doi.org/10.1111/ijd.13795 |
| [12] | Kussainova, A., Kassym, L., Akhmetova, A., et al. (2020) Vitiligo and Anxiety: A Systematic Review and Meta-Analysis. PLOS ONE, 15, e0241445. https://doi.org/10.1371/journal.pone.0241445 |
| [13] | Lin, F., Hu, W., Xu, W., et al. (2021) CXCL9 as a Key Biomarker of Vitiligo Activity and Prediction of the Success of Cultured Melanocyte Transplantation. Scientific Reports, 11, Article No. 18298. https://doi.org/10.1038/s41598-021-97296-2 |
| [14] | Migayron, L., Boniface, K. and Seneschal, J. (2020) Vitiligo, from Physiopathology to Emerging Treatments: A Review. Dermatologic Therapy (Heidelb), 10, 1185-1198. https://doi.org/10.1007/s13555-020-00447-y |
| [15] | Mosenson, J., Flood, K., Klarquist, J., et al. (2014) Preferential Secretion of Inducible HSP70 by Vitiligo Melanocytes under Stress. Pigment Cell & Melanoma Research, 27, 209-220. https://doi.org/10.1111/pcmr.12208 |
| [16] | Nigam, P., Patra, P., Khodiar, P., et al. (2011) A Study of Blood CD3 , CD4 , and CD8 T Cell Levels and CD4 :CD8 Ratio in Vitiligo Patients. Indian Journal of Dermatology, Venereology and Leprology, 77, 111. https://doi.org/10.4103/0378-6323.74993 |
| [17] | Qian, Y., Liu, X., Sun, H., et al. (2022) Urinary Proteomics Analysis of Active Vitiligo Patients: Biomarkers for Steroid Treatment Efficacy Prediction and Monitoring. Frontiers in Molecular Biosciences, 9, Article ID: 761562. https://doi.org/10.3389/fmolb.2022.761562 |
| [18] | Raam, L., Kaleviste, E., ？unina, M., et al. (2018) Lymphoid Stress Surveillance Response Contributes to Vitiligo Pathogenesis. Frontiers in Immunology, 9, Article No. 2707. https://doi.org/10.3389/fimmu.2018.02707 |
| [19] | Bleuel, R., et al. (2018) Therapeutic Management of Vitiligo. Journal Der Deutschen Dermatologischen Gesellschaft, 16, 1309-1313. https://doi.org/10.1111/ddg.13680 |
| [20] | Said-Fernandez, S., Sanchez-Domínguez, C., Salinas-Santander, M., et al. (2021) Novel Immunological and Genetic Factors Associated with Vitiligo: A Review. Experimental and Therapeutic Medicine, 21, Article No. 312. https://doi.org/10.3892/etm.2021.9743 |
| [21] | Speeckaert, R., Dugardin, J., Lambert, J., et al. (2018) Critical Appraisal of the Oxidative Stress Pathway in Vitiligo: A Systematic Review and Meta-Analysis. Journal of the European Academy of Dermatology and Venereology, 32, 1089-1098. https://doi.org/10.1111/jdv.14792 |
| [22] | Tomaszewska, K., Koz？owska, M., Kaszuba, A., et al. (2020) Increased Serum Levels of IFN-γ, IL-1β, and IL-6 in Patients with Alopecia Areata and Nonsegmental Vitiligo. Oxidative Medicine and Cellular Longevity, 2020, Article ID: 5693572. https://doi.org/10.1155/2020/5693572 |
| [23] | Tulic, M., Cavazza, E., Cheli, Y., et al. (2019) Innate Lymphocyte-Induced CXCR3B-Mediated Melanocyte Apoptosis Is a Potential Initiator of T-Cell Autoreactivity in Vitiligo. Nature Communications, 10, Article No. 2178. https://doi.org/10.1038/s41467-019-09963-8 |
