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黏膜相关恒定T细胞的激活状态反映系统性红斑狼疮的疾病活动和病理情况。

Activation status of mucosal-associated invariant T cells reflects disease activity and pathology of systemic lupus erythematosus.

作者信息

Chiba Asako, Tamura Naoto, Yoshikiyo Kazunori, Murayama Goh, Kitagaichi Mie, Yamaji Ken, Takasaki Yoshinari, Miyake Sachiko

机构信息

Department of Immunology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.

Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan.

出版信息

Arthritis Res Ther. 2017 Mar 14;19(1):58. doi: 10.1186/s13075-017-1257-5.

Abstract

BACKGROUND

Mucosal-associated invariant T (MAIT) cells are innate-like lymphocytes constituting a large proportion of peripheral blood T cells expressing αβ T-cell receptor in humans. In this study, we aimed to investigate their involvement in systemic lupus erythematosus (SLE).

METHODS

Peripheral blood MAIT cells from patients with SLE were assessed for their frequency, activation markers, and cell death by flow cytometry. The correlation between plasma cytokine levels and CD69 expression on MAIT cells was analyzed. The major histocompatibility complex class I-related protein MR1-restricted antigen-presenting capacity of antigen-presenting cells was investigated. Cytokine-mediated activation of MAIT cells in the absence of exogenous antigens was also examined.

RESULTS

The frequency of MAIT cells was markedly reduced in SLE. The reduced number of MAIT cells was not attributable to the downregulation of surface markers, but it was partially due to the enhanced cell death of MAIT cells, possibly by activation-induced cell death. The CD69 expression levels on MAIT cells in SLE correlated with disease activity. Moreover, monocytes from patients with SLE exhibited increased ability to induce MAIT cell activation. The plasma concentration of interleukin (IL)-6, IL-18, and interferon (IFN)-α positively correlated with the expression levels of CD69 on MAIT cells in SLE. MAIT cells were activated by cytokines, including IFN-α, IL-15, and IL-12 plus IL-18, in the absence of exogenous antigens.

CONCLUSIONS

These results suggest that MAIT cells reflect the pathological condition of SLE and that their activated status correlates with presence of disease.

摘要

背景

黏膜相关恒定T(MAIT)细胞是一类固有样淋巴细胞,在人类外周血中表达αβT细胞受体的T细胞中占很大比例。在本研究中,我们旨在探究它们在系统性红斑狼疮(SLE)中的作用。

方法

通过流式细胞术评估SLE患者外周血MAIT细胞的频率、活化标志物和细胞死亡情况。分析血浆细胞因子水平与MAIT细胞上CD69表达之间的相关性。研究抗原呈递细胞的主要组织相容性复合体I类相关蛋白MR1限制的抗原呈递能力。还检测了在无外源性抗原情况下细胞因子介导的MAIT细胞活化。

结果

SLE患者中MAIT细胞的频率显著降低。MAIT细胞数量减少并非归因于表面标志物的下调,而是部分由于MAIT细胞的细胞死亡增强,可能是通过活化诱导的细胞死亡。SLE患者MAIT细胞上的CD69表达水平与疾病活动相关。此外,SLE患者的单核细胞诱导MAIT细胞活化的能力增强。SLE患者血浆中白细胞介素(IL)-6、IL-18和干扰素(IFN)-α的浓度与MAIT细胞上CD69的表达水平呈正相关。在无外源性抗原的情况下,MAIT细胞可被包括IFN-α、IL-15以及IL-12加IL-18在内的细胞因子激活。

结论

这些结果表明MAIT细胞反映了SLE的病理状况,且其活化状态与疾病的存在相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c194/5348792/fffabe0f5924/13075_2017_1257_Fig1_HTML.jpg

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