LL37-DNA Complex Drives Vitiligo Progression Through TLR9-MyD88 Signaling Pathways.

IF 3.9 3区 医学 Q2 CELL BIOLOGY Pigment Cell & Melanoma Research Pub Date : 2024-09-30 DOI:10.1111/pcmr.13202
Jingying Wang, Hanxiao Mao, Rulan Liu, Ziyuan Zeng, Lvsha Xie, Yan Yang, Yuanmin He
{"title":"LL37-DNA Complex Drives Vitiligo Progression Through TLR9-MyD88 Signaling Pathways.","authors":"Jingying Wang, Hanxiao Mao, Rulan Liu, Ziyuan Zeng, Lvsha Xie, Yan Yang, Yuanmin He","doi":"10.1111/pcmr.13202","DOIUrl":null,"url":null,"abstract":"<p><p>Vitiligo is an autoimmune disorder characterized by chronic depigmentation and milk-white patches on the skin. Skin infiltration by autoreactive CD8<sup>+</sup> T cells causes melanocyte destruction in vitiligo. Multiple risk factors, particularly immune-related inflammatory factors, are involved in the disappearance of melanocytes. LL37 is a classic damage-associated molecular pattern molecule that is involved in the development of various autoimmune diseases. An enhanced expression of LL37 in vitiligo is known; however, the exact role of LL37 in melanocyte loss has not yet been elucidated. In the present study, we detected increased LL37 expression in vitiligo serum and lesions. Furthermore, we confirmed that cultured keratinocytes released LL37 after treatment with H<sub>2</sub>O<sub>2</sub>. Moreover, the LL37-DNA complex enhanced the secretion of CXCL9, CXCL10, and CXCL16 from keratinocytes via the TLR9-MyD88 signaling pathway and facilitated the migration of CD8<sup>+</sup> T cells. Altogether, our study demonstrates that LL37 released from keratinocytes binds to DNA and contributes to melanocyte destruction under oxidative stress-induced autoimmunity in vitiligo.</p>","PeriodicalId":219,"journal":{"name":"Pigment Cell & Melanoma Research","volume":" ","pages":""},"PeriodicalIF":3.9000,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pigment Cell & Melanoma Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/pcmr.13202","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Vitiligo is an autoimmune disorder characterized by chronic depigmentation and milk-white patches on the skin. Skin infiltration by autoreactive CD8+ T cells causes melanocyte destruction in vitiligo. Multiple risk factors, particularly immune-related inflammatory factors, are involved in the disappearance of melanocytes. LL37 is a classic damage-associated molecular pattern molecule that is involved in the development of various autoimmune diseases. An enhanced expression of LL37 in vitiligo is known; however, the exact role of LL37 in melanocyte loss has not yet been elucidated. In the present study, we detected increased LL37 expression in vitiligo serum and lesions. Furthermore, we confirmed that cultured keratinocytes released LL37 after treatment with H2O2. Moreover, the LL37-DNA complex enhanced the secretion of CXCL9, CXCL10, and CXCL16 from keratinocytes via the TLR9-MyD88 signaling pathway and facilitated the migration of CD8+ T cells. Altogether, our study demonstrates that LL37 released from keratinocytes binds to DNA and contributes to melanocyte destruction under oxidative stress-induced autoimmunity in vitiligo.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
LL37-DNA复合物通过TLR9-MyD88信号通路驱动白癜风进展
白癜风是一种自身免疫性疾病,其特征是皮肤上出现慢性色素脱失和乳白色斑块。自体反应性 CD8+ T 细胞对皮肤的浸润导致白癜风患者黑色素细胞的破坏。黑色素细胞的消失涉及多种危险因素,尤其是与免疫相关的炎症因素。LL37 是一种典型的损伤相关分子模式分子,与各种自身免疫性疾病的发生有关。众所周知,LL37 在白癜风中的表达增强;然而,LL37 在黑色素细胞脱失中的确切作用尚未阐明。在本研究中,我们检测到 LL37 在白癜风血清和皮损中的表达增加。此外,我们还证实培养的角质细胞在经 H2O2 处理后会释放 LL37。此外,LL37-DNA 复合物通过 TLR9-MyD88 信号通路增强了角朊细胞分泌的 CXCL9、CXCL10 和 CXCL16,并促进了 CD8+ T 细胞的迁移。总之,我们的研究表明,在氧化应激诱导的白癜风自身免疫作用下,从角质形成细胞释放的LL37可与DNA结合并导致黑色素细胞破坏。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Pigment Cell & Melanoma Research
Pigment Cell & Melanoma Research 医学-皮肤病学
CiteScore
8.90
自引率
2.30%
发文量
54
审稿时长
6-12 weeks
期刊介绍: Pigment Cell & Melanoma Researchpublishes manuscripts on all aspects of pigment cells including development, cell and molecular biology, genetics, diseases of pigment cells including melanoma. Papers that provide insights into the causes and progression of melanoma including the process of metastasis and invasion, proliferation, senescence, apoptosis or gene regulation are especially welcome, as are papers that use the melanocyte system to answer questions of general biological relevance. Papers that are purely descriptive or make only minor advances to our knowledge of pigment cells or melanoma in particular are not suitable for this journal. Keywords Pigment Cell & Melanoma Research, cell biology, melatonin, biochemistry, chemistry, comparative biology, dermatology, developmental biology, genetics, hormones, intracellular signalling, melanoma, molecular biology, ocular and extracutaneous melanin, pharmacology, photobiology, physics, pigmentary disorders
期刊最新文献
The Lipid Droplet Protein DHRS3 Is a Regulator of Melanoma Cell State. UVA Irradiation Promotes Melanoma Cell Proliferation Mediated by OPN3 Independently of ROS Production. Issue Information Bay 11-7082, an NF-κB Inhibitor, Prevents Post-Inflammatory Hyperpigmentation Through Inhibition of Inflammation and Melanogenesis. Low-Dose Baricitinib Plus Narrow-Band Ultraviolet B for the Treatment of Progressive Non-Segmental Vitiligo: A Prospective, Controlled, Open-Label Study.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1