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Fas 之谜未解:干燥综合征患者单核细胞可能难以死亡。

Unsolved mystery of Fas: mononuclear cells may have trouble dying in patients with Sjögren's syndrome.

机构信息

Department of Dentistry, Faculty of Medicine in Hradec Kralove, Charles University and University Hospital, Sokolska 581, 500 05, Hradec Kralove, Czech Republic.

Department of Clinical Immunology and Allergology, Faculty of Medicine in Hradec Kralove, Charles University, Simkova 870, 500 03, Hradec Kralove, Czech Republic.

出版信息

BMC Immunol. 2023 Jun 23;24(1):12. doi: 10.1186/s12865-023-00544-5.

Abstract

BACKGROUND

Patients with Sjögren's syndrome, like other patients with autoimmune disorders, display dysregulation in the function of their immune system. Fas and Fas Ligand (FasL) are among the dysregulated proteins.

METHODS

We studied Fas and FasL on IL-2Rα cells and in serum of patients with Sjögren's syndrome (n = 16) and healthy individuals (n = 16); both from same ethnic and geographical background. We used flow cytometry and enzyme-linked immunosorbent for this purpose. We also measured the expression of Bcl-2 and Bax by reverse transcription quantitative real-time PCR (RT-qPCR) and percentage of apoptotic and dead cells using Annexin V and 7-AAD staining in lymphocytes.

RESULTS

FasL was increased in patients' T and B cells while Fas was increased in patients' monocytes, T and B cells. No signs of increased apoptosis were found. sFas and sFasL in patients' serum were increased, although the increase in sFasL was not significant. We suspect an effect of non-steroidal anti-inflammatory therapy on B cells, explaining the decrease of the percentage Fas B cells found within our samples. In healthy individuals, there was a noticeable pattern in the expression of FasL which mutually correlated to populations of mononuclear cells; this correlation was absent in the patients with Sjögren's syndrome.

CONCLUSIONS

Mononuclear cells expressing IL-2Rα had upregulated Fas in Sjögren's syndrome. However, the rate of apoptosis based on Annexin V staining and the Bcl-2/Bax expression was not observed in mononuclear cells. We suspect a functional role of abnormal levels of Fas and FasL which has not been cleared yet.

摘要

背景

干燥综合征患者与其他自身免疫性疾病患者一样,其免疫系统功能失调。Fas 和 Fas 配体(FasL)就是失调蛋白之一。

方法

我们研究了干燥综合征患者(n=16)和健康个体(n=16)的 IL-2Rα 细胞和血清中的 Fas 和 FasL;两者具有相同的种族和地理背景。我们使用流式细胞术和酶联免疫吸附法进行了这项研究。我们还通过逆转录定量实时 PCR(RT-qPCR)测量了 Bcl-2 和 Bax 的表达,并通过 Annexin V 和 7-AAD 染色测量了淋巴细胞中凋亡和死亡细胞的百分比。

结果

患者的 T 和 B 细胞中 FasL 增加,而单核细胞、T 和 B 细胞中 Fas 增加。未发现凋亡增加的迹象。患者血清中的 sFas 和 sFasL 增加,尽管 sFasL 的增加并不显著。我们怀疑非甾体抗炎治疗对 B 细胞有影响,这解释了我们样本中 FasB 细胞百分比下降的原因。在健康个体中,FasL 的表达存在明显的模式,与单核细胞群体相互关联;而在干燥综合征患者中则不存在这种关联。

结论

干燥综合征患者的表达 IL-2Rα 的单核细胞中 Fas 上调。然而,在单核细胞中未观察到基于 Annexin V 染色的凋亡率和 Bcl-2/Bax 表达。我们怀疑异常 Fas 和 FasL 水平具有尚未阐明的功能作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e11c/10288785/d6de02c8ee3b/12865_2023_544_Fig1_HTML.jpg

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