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ISG15-USP18 Dysregulation by Oxidative Stress Promotes IFN-γ Secretion from CD8+ T Cells in Vitiligo

Authors
 Eun Jung Lee  ;  Ji Young Kim  ;  Joo Hye Yeo  ;  Sujin Park  ;  Yu Jeong Bae  ;  Il Joo Kwon  ;  Seol Hwa Seong  ;  Jinu Lee  ;  Sang Ho Oh 
Citation
 JOURNAL OF INVESTIGATIVE DERMATOLOGY, Vol.144(2) : 273-283.e11, 2024-02 
Journal Title
JOURNAL OF INVESTIGATIVE DERMATOLOGY
ISSN
 0022-202X 
Issue Date
2024-02
MeSH
Autoimmune Diseases* / pathology ; CD8-Positive T-Lymphocytes / metabolism ; Cytokines / metabolism ; Humans ; Hypopigmentation* / pathology ; Melanocytes / metabolism ; Oxidative Stress / physiology ; Skin / pathology ; Ubiquitin Thiolesterase / genetics ; Ubiquitin Thiolesterase / metabolism ; Ubiquitins / metabolism ; Vitiligo* / pathology
Abstract
Excessive oxidative stress is thought to play pathologic roles in cellular senescence and autoimmune disorders by inducing inflammation and breaking down immune tolerance. In this study, we sought to identify the factors linking oxidative stress to autoimmunity and cellular senescence in vitiligo, where elevated oxidative stress plays an important role. RNA sequencing analysis of hydrogen peroxide-treated melanocytes revealed upregulation of ISG15. The upregulation of ISG15 was observed in vitiligo skin tissues as well as in the blood of patients with vitiligo, whereas USP18 downregulation was observed in vitiligo melanocytes and vitiligo skin tissues. Oxidative stress induced hypermethylation of the USP18 promoter region in keratinocytes and melanocytes, and USP18 promoter hypermethylation was also confirmed in vitiligo skin tissues. Our results indicate that USP18 promoter hypermethylation caused by oxidative stress increases ISG15 expression in keratinocytes and melanocytes along with senescence changes, leading CD8+ T cells to produce IFN-γ, the main pathogenic cytokine in vitiligo. Therefore, the ISG15-USP18 network may be important in oxidative stress-induced autoimmunity and cellular senescence in vitiligo pathogenesis.
Full Text
https://www.sciencedirect.com/science/article/pii/S0022202X23025186
DOI
10.1016/j.jid.2023.08.006
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
Yonsei Authors
Kwon, Il Joo(권일주)
Park, Sujin(박수진)
Seong, Seol Hwa(성설화)
Oh, Sang Ho(오상호) ORCID logo https://orcid.org/0000-0002-4477-1400
Lee, Eun Jung(이은정) ORCID logo https://orcid.org/0000-0002-8401-2652
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/198635
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