Oxidative Stress-Induced HMGB1 Release from Melanocytes: A Paracrine Mechanism Underlying the Cutaneous Inflammation in Vitiligo.

Abstract

Vitiligo is a cutaneous depigmentation disorder caused by the destruction of epidermal melanocytes. The generation and the skin infiltration of autoreactive CD8+ cytotoxic T cells triggered by oxidative stress play a critical role in vitiligo. High-mobility group protein B1 (HMGB1) is a classic damage-associated molecular pattern molecule with strong proinflammatory effects in inflammatory reactions. A previous study reported an enhanced expression of HMGB1 in vitiligo lesions, but the role of HMGB1 in cutaneous inflammation of vitiligo is still unknown. In the present study, we initially found that HMGB1 was released from the nucleus of melanocytes in vitiligo perilesional skin. Furthermore, cultured normal human melanocytes could release HMGB1 under treatment with hydrogen peroxide. Moreover, HMGB1 facilitated the secretion of CXCL16 and IL-8 from keratinocytes by binding to the receptor for advanced glycation end products and activating NF-κB and extracellular signal-regulated kinase signaling pathways. Subsequently, HMGB1 led to the formation of chemotaxis for the migration of CD8+ T cells from patients with vitiligo by increasing the release of CXCL16 from keratinocytes. Additionally, HMGB1 promoted the maturation of dendritic cells from patients with vitiligo. Altogether, our study demonstrates that HMGB1 released from melanocytes contributes to the formation of oxidative stress-induced autoimmunity in vitiligo.

• Authors: Tingting Cui, Weigang Zhang, Shuli Li, Xuguang Chen, Yuqian Chang, Xiuli Yi, Pan Kang, Yuqi Yang, Jiaxi Chen, Ling Liu, Zhe Jian, Kai Li, Gang Wang, Tianwen Gao, Pu Song, Chunying Li
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 139 Issue 10 Pg. 2174-2184.e4 (10 2019) ISSN: 1523-1747 [Electronic] United States
• PMID: 30998983 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Chemokine CXCL1
• HMGB1 Protein

Topics

• Autoimmunity (genetics)
• Blotting, Western (methods)
• CD8-Positive T-Lymphocytes (metabolism)
• Case-Control Studies
• Cell Movement (immunology)
• Cells, Cultured
• Chemokine CXCL1 (metabolism)
• Enzyme-Linked Immunosorbent Assay (methods)
• Flow Cytometry (methods)
• HMGB1 Protein (metabolism)
• Humans
• Hypopigmentation (genetics, pathology)
• Keratinocytes (metabolism)
• Melanocytes (metabolism)
• Oxidative Stress (physiology)
• Real-Time Polymerase Chain Reaction (methods)
• Reference Values
• Vitiligo (blood, genetics, immunology, pathology)