Oxidative stress drives CD8~+T cells skin trafficking in vitiligo via CXCL16 upregulation by activating the unfolded protein response in keratinocytes
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- 英文论文题名：Oxidative stress drives CD8~+T cells skin trafficking in vitiligo via CXCL16 upregulation by activating the unfolded protein response in keratinocytes
- 论文作者：Li Shuli ; Zhu Guannan ; Yang Yuqi ; Jian Zhe ; Guo Sen ; Dai Wei ; Shi Qiong ; Ge Rui ; Ma Jingjing ; Liu Ling ; Li Kai ; Luan Qi ; Wang Gang ; Gao Tianwen ; Li Chunying
- 英文论文作者：Li Shuli ; Zhu Guannan ; Yang Yuqi ; Jian Zhe ; Guo Sen ; Dai Wei ; Shi Qiong ; Ge Rui ; Ma Jingjing ; Liu Ling ; Li Kai ; Luan Qi ; Wang Gang ; Gao Tianwen ; Li Chunying ; Department of Dermatology ; Xijing Hospital ; Fourth Military Medical University
- 年：2016
- 作者机构：Department of Dermatology,Xijing Hospital,Fourth Military Medical University;
- 英文论文关键词：Oxidative stress ; unfolded protein response(UPR) ; CXCL16 ; CXCR6 ; CD8+T cells ; skin migration
- 会议召开时间：2016-11-04
- 会议录名称：第十一届全国免疫学学术大会摘要汇编
- 英文会议录名称：Abstracts of 2016 CSI Congress on Immunology
- 语种：英文
- 分类号：R758.41
- 学会代码：IGMD
- 会议名称：第十一届全国免疫学学术大会
- 会议地点：中国安徽合肥
- 主办单位：中国免疫学会
- 学会名称：中国免疫学会
- 页数：1
- 文件大小：1011k
- 原文格式：D
- 会议级别：全国
摘要
Background: In vitiligo, elevated reactive oxygen species(ROS) have been proven as a key player during disease initiation and progression in melanocytes. Nevertheless, little is known about the effects of ROS on other cells involved in the aberrant microenvironment e.g. keratinocytes and the following immune events. CXCL16 is constitutively expressed in keratinocytes and recently found to mediate homing of CD8~+T cells in human skin.Objective: To explicate the effect of oxidative stress on human keratinocyte and its capacity to drive CD8~+T cell trafficking via CXCL16 regulation.Methods: We first detected putative T cells skin homing chemokines and ROS level in vitiligo serum and lesions. The production of candidate chemokines was detected by q RT-PCR and ELISA in keratinocytes exposed to H_2O_2. Furthermore, mediators involved were analyzed by q RT-PCR, western blot, ELISA and immunofluorescence. Next, we tested the chemotactic migration of vitiligo CD8~+T cells mediated by CXCL16–CXCR6 pair by transwell assay.Results: CXCL16 expression increased and showed a positive correlation with oxidative stress level in vitiligo serum and lesions. The H_2O_2–induced CXCL16 expression was due to the activation of 2 unfolded protein response pathways, PERK–e IF2α and IRE1α–XBP1. CXCL16 produced by stressed keratinocytes induced migration of CXCR6~+CD8~+T cells derived from vitiligo patients. CXCR6~+CD8~+T cells skin infiltration is accompanied by melanocytes loss in vitiligo lesions.Conclusion: Our study demonstrated that CXCL16–CXCR6 mediates CD8~+T cell skin trafficking under oxidative stress in vitiligo. The CXCL16 expression in human keratinocytes induced by ROS is, at least partially, by UPR activation.
Background: In vitiligo, elevated reactive oxygen species(ROS) have been proven as a key player during disease initiation and progression in melanocytes. Nevertheless, little is known about the effects of ROS on other cells involved in the aberrant microenvironment e.g. keratinocytes and the following immune events. CXCL16 is constitutively expressed in keratinocytes and recently found to mediate homing of CD8~+T cells in human skin.Objective: To explicate the effect of oxidative stress on human keratinocyte and its capacity to drive CD8~+T cell trafficking via CXCL16 regulation.Methods: We first detected putative T cells skin homing chemokines and ROS level in vitiligo serum and lesions. The production of candidate chemokines was detected by q RT-PCR and ELISA in keratinocytes exposed to H_2O_2. Furthermore, mediators involved were analyzed by q RT-PCR, western blot, ELISA and immunofluorescence. Next, we tested the chemotactic migration of vitiligo CD8~+T cells mediated by CXCL16–CXCR6 pair by transwell assay.Results: CXCL16 expression increased and showed a positive correlation with oxidative stress level in vitiligo serum and lesions. The H_2O_2–induced CXCL16 expression was due to the activation of 2 unfolded protein response pathways, PERK–e IF2α and IRE1α–XBP1. CXCL16 produced by stressed keratinocytes induced migration of CXCR6~+CD8~+T cells derived from vitiligo patients. CXCR6~+CD8~+T cells skin infiltration is accompanied by melanocytes loss in vitiligo lesions.Conclusion: Our study demonstrated that CXCL16–CXCR6 mediates CD8~+T cell skin trafficking under oxidative stress in vitiligo. The CXCL16 expression in human keratinocytes induced by ROS is, at least partially, by UPR activation.
Background: In vitiligo, elevated reactive oxygen species(ROS) have been proven as a key player during disease initiation and progression in melanocytes. Nevertheless, little is known about the effects of ROS on other cells involved in the aberrant microenvironment e.g. keratinocytes and the following immune events. CXCL16 is constitutively expressed in keratinocytes and recently found to mediate homing of CD8~+T cells in human skin.Objective: To explicate the effect of oxidative stress on human keratinocyte and its capacity to drive CD8~+T cell trafficking via CXCL16 regulation.Methods: We first detected putative T cells skin homing chemokines and ROS level in vitiligo serum and lesions. The production of candidate chemokines was detected by q RT-PCR and ELISA in keratinocytes exposed to H_2O_2. Furthermore, mediators involved were analyzed by q RT-PCR, western blot, ELISA and immunofluorescence. Next, we tested the chemotactic migration of vitiligo CD8~+T cells mediated by CXCL16–CXCR6 pair by transwell assay.Results: CXCL16 expression increased and showed a positive correlation with oxidative stress level in vitiligo serum and lesions. The H_2O_2–induced CXCL16 expression was due to the activation of 2 unfolded protein response pathways, PERK–e IF2α and IRE1α–XBP1. CXCL16 produced by stressed keratinocytes induced migration of CXCR6~+CD8~+T cells derived from vitiligo patients. CXCR6~+CD8~+T cells skin infiltration is accompanied by melanocytes loss in vitiligo lesions.Conclusion: Our study demonstrated that CXCL16–CXCR6 mediates CD8~+T cell skin trafficking under oxidative stress in vitiligo. The CXCL16 expression in human keratinocytes induced by ROS is, at least partially, by UPR activation.
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