1. Academic Validation
  2. Oxidative stress-induced IL-15 trans-presentation in keratinocytes contributes to CD8+ T cells activation via JAK-STAT pathway in vitiligo

Oxidative stress-induced IL-15 trans-presentation in keratinocytes contributes to CD8+ T cells activation via JAK-STAT pathway in vitiligo

  • Free Radic Biol Med. 2019 Aug 1;139:80-91. doi: 10.1016/j.freeradbiomed.2019.05.011.
Xuguang Chen 1 Weinan Guo 1 Yuqian Chang 1 Jiaxi Chen 1 Pan Kang 1 Xiuli Yi 1 Tingting Cui 1 Sen Guo 1 Qian Xiao 1 Zhe Jian 1 Kai Li 1 Tianwen Gao 1 Shuli Li 2 Ling Liu 3 Chunying Li 4
Affiliations

Affiliations

  • 1 Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
  • 2 Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China. Electronic address: xjpf10@fmmu.edu.cn.
  • 3 Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China. Electronic address: vanilla@fmmu.edu.cn.
  • 4 Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China. Electronic address: lichying@fmmu.edu.cn.
Abstract

Oxidative stress and effector memory CD8+ T cells have been greatly implicated in vitiligo pathogenesis. However, the crosstalk between these two crucial pathogenic factors has been merely investigated. IL-15 has been regarded as an important cytokine exerting its facilitative effect on memory CD8+ T cells function in various autoimmune diseases. In the present study, we initially discovered that the IL-15 expression was significantly increased in vitiligo epidermis and highly associated with epidermal H2O2 content. In addition, epidermal IL-15 expression was mainly derived from keratinocytes. Then, we showed that oxidative stress promoted IL-15 and IL-15Rα expression as well as IL-15 trans-presentation by activating NF-κB signaling in keratinocytes. What's more, the trans-presented IL-15, rather than the secreted one, was accounted for the potentiation of CD8+ TEMs activation. We further investigated the mechanism underlying trans-presented IL-15 in potentiating CD8+ TEMs activation and found that the blockage of IL-15-JAK-STAT signaling could be a potent therapeutic approach. Taken together, our results demonstrate that oxidative stress-induced IL-15 trans-presentation in keratinocytes contributes to the activation of CD8+ TEMs, providing a novel mechanism by which oxidative stress initiates autoimmunity in vitiligo.

Keywords

CD8(+) T cell; IL-15; Keratinocyte; Oxidative stress; Vitiligo.

Figures
Products