Enhancement of CD8+T cell cytotoxicity activity by IFN-α implies alternative pathologic role in systemic lupus erythematosus

IF 4.7 Q2 IMMUNOLOGY
Chen-xing Zhang , You-ying Mao , Yu-pin Tan , Mei-yu Zhang , Kang Shao , Shu-jun Wang , Ping Ji , Jia-yuan Wang , Lei Yin , Ying Wang
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引用次数: 0

Abstract

Objective

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease which is affected by the environmental, genetic factors as well as the immune system. Previous reports have implicated IFN-α in the pathogenesis of SLE. Up to date, however, no research has ever investigated the effect of IFN-α on CD8+T cells, which might be implicated in the pathogenesis of SLE. In the present study, we aimed to explore the pathologic role of IFN-α in regard to dysfunction of CD8+T cells in SLE.

Methods

Serum level of IFN-α was detected in SLE and healthy controls (HC). Surface expression of lysosome-associated membrane protein 1 (LAMP-1; CD107a) and secretion of granzyme B of CD8+T cells was measured in SLE and HC with or without IFN-α co-stimulation/PI3K inhibitor.

Results

Our results demonstrated that there was increased surface expression of CD107a of CD8+T cells in SLE patients compared with healthy controls (HC), indicating enhanced cytotoxicity of CD8+T cells in SLE patients. Meanwhile, increased secretion of granzyme B was also detected in CD8+T cells of SLE compared with HC, which correlated with the disease activity (SLEDAI). Furthermore, elevated serum level of IFN-α in SLE was confirmed in our study. In vitro study, granzyme B secretion by CD8+T cells was upregulated upon IFN-α costimulation, which was consistent with enhanced cytotoxicity of CD8+T cells upon IFN-α costimulation, as reflected by elevated surface expression of CD107a. PI3K inhibitor reversed increased granzyme B synthesis upon IFN-α costimulation in a dose-dependent manner.

Conclusion

In summary, elevated serum level of IFN-α was responsible for increased secretion of granzyme B and enhanced cytotoxicity of CD8+T cells in SLE and this process may be related to PI3K pathway. Relevant molecules and mechanism remains to be explored in the future.
IFN-α增强CD8+T细胞毒性活性提示系统性红斑狼疮的病理作用
目的系统性红斑狼疮(SLE)是一种受环境、遗传和免疫系统共同影响的异质自身免疫性疾病。先前的报道暗示IFN-α参与SLE的发病机制。然而,到目前为止,还没有研究研究IFN-α对CD8+T细胞的影响,这可能与SLE的发病机制有关。在本研究中,我们旨在探讨IFN-α在SLE中CD8+T细胞功能障碍中的病理作用。方法检测SLE患者和健康对照组(HC)血清IFN-α水平。溶酶体相关膜蛋白1 (LAMP-1)表面表达;在有或没有IFN-α共刺激/PI3K抑制剂的SLE和HC中检测CD107a)和CD8+T细胞颗粒酶B的分泌。结果与健康对照(HC)相比,SLE患者CD8+T细胞表面CD107a表达增加,表明SLE患者CD8+T细胞的细胞毒性增强。与HC相比,SLE的CD8+T细胞中颗粒酶B的分泌也有所增加,与疾病活动性相关(SLEDAI)。此外,我们的研究证实SLE患者血清中IFN-α水平升高。体外研究发现,IFN-α共刺激后CD8+T细胞颗粒酶B分泌上调,这与IFN-α共刺激后CD8+T细胞的细胞毒性增强一致,表现为CD107a表面表达升高。PI3K抑制剂以剂量依赖的方式逆转IFN-α共刺激下颗粒酶B合成的增加。综上所述,血清IFN-α水平升高导致SLE颗粒酶B分泌增加,CD8+T细胞毒性增强,这一过程可能与PI3K通路有关。相关分子及其作用机制有待进一步研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Translational Autoimmunity
Journal of Translational Autoimmunity Medicine-Immunology and Allergy
CiteScore
7.80
自引率
2.60%
发文量
33
审稿时长
55 days
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