Immunomodulatory effects of sleep deprivation at different timing of psoriasiform process on skin inflammation
Immunomodulatory effects of sleep deprivation at different timing of psoriasiform process on skin inflammation
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银屑病过程不同时间睡眠剥夺对皮肤炎症的免疫调节作用
DOI：
10.1016/j.bbrc.2019.03.185
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发表时间：
2019
影响因子：
3.1
通讯作者：
Zheng Jie
中科院分区：
文献类型：
--
作者：
Yang Hui;Li Xia;Zhang Li;Xue Feng;Zheng Jie
睡眠不足会影响牛皮癣等免疫性炎症性皮肤病的病理生理。越来越多的努力指向探索涉及睡眠剥夺和免疫反应的潜在机制。然而，关注不同睡眠剥夺时间对皮肤炎症影响的研究还很缺乏。因此，本研究探讨了在银屑病样小鼠模型中，在银屑病形成过程的不同时间剥夺睡眠（PS）对皮肤炎症的免疫调节作用。成年雄性C57BL / 6小鼠被分为5组(n = 5):对照组(CON) IMQ-S2组(治疗与31.25毫克咪喹莫特(IMQ) 5天每天48 h (PS剥夺第四和第五天],S2-IMQ组(治疗5天每天31.25毫克IMQ 48 h的PS剥夺第一和第二天),31.25组(治疗5天每天31.25毫克IMQ)和62.5组(治疗62.5毫克每天IMQ 5天)。与IMQ-S2组和31.25组比较，S2-IMQ组小鼠皮损及淋巴结IL-17A mRNA水平显著升高，皮肤炎症反应加重。而IMQ-S2组皮肤病变组织中IL-1β mRNA水平最高，淋巴结组织中IL-6 mRNA水平最高。流式细胞术结果显示，S2-IMQ组淋巴结中γδT细胞、IL-17A+γδT细胞、树突状细胞（DC）和MHCⅡ+ DC的频率显著高于IMQ-S2组和31.25组，皮损处γδT细胞的频率也显著高于IMQ-S2组和31.25组。然而，S2-IMQ组皮肤病变中dc的发生频率明显低于IMQ-S2组。这些数据表明，PS剥夺在银屑病早期而不是晚期通过调节免疫系统加剧皮肤炎症，这可能涉及到PS剥夺刺激IL-1β和IL-6反过来通过激活和增殖γδT细胞和dc迁移增加IL-17的表达。
Sleep deprivation affects the pathophysiology of immune-inflammatory skin diseases such as psoriasis. Increasing efforts are directed toward exploring potential mechanisms involving sleep deprivation and immune responses. However, studies focusing on the effects of different timing of sleep deprivation on skin inflammation are lacking. This study thus investigated the immunomodulatory effects of paradoxical sleep (PS) deprivation at different timing of psoriasiform process on skin inflammation in the psoriasis-like mouse model. Male adult C57BL/6 mice were divided into 5 groups (each n = 5): control group (CON), IMQ-S2 group [treating with 31.25 mg imiquimod (IMQ) per day for 5 days with 48 h of PS deprivation on the fourth and fifth day], S2-IMQ group (treating with 31.25 mg IMQ per day for 5 days with 48 h of PS deprivation on the first and second day), 31.25 group (treating with 31.25 mg IMQ per day for 5 days) and 62.5 group (treating with 62.5 mg IMQ per day for 5 days). Compared with IMQ-S2 group and 31.25 group, S2-IMQ group mice had significant increase of IL-17A mRNA level in skin lesions and lymph nodes, and more severe cutaneous inflammation. However, IMQ-S2 group had the highest IL-1β mRNA level in skin lesions and the highest IL-6 mRNA level in lymph nodes among the three groups. Results of flow cytometry showed that frequencies of γδT cell, IL-17A+γδT cell, dendritic cell (DC) and MHCⅡ+ DC in lymph nodes of S2-IMQ group were significantly higher than IMQ-S2 group and 31.25 group, so was the frequency of γδT cells in skin lesions. However, the frequency of DCs in skin lesions of S2-IMQ group was significantly lower than IMQ-S2 group. These data suggest that PS deprivation at the early stage rather than the late stage of psoriasiform process exacerbates the skin inflammation through modulation of the immune system, which may involve that IL-1β and IL-6 stimulated by PS deprivation in turn increasing IL-17 expression through activation and proliferation of γδT cells and DCs migration.