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CX3CR1+CD8 T 细胞与干燥综合征和 IgG4 相关疾病的衰老及不同临床特征显著相关。

Significant association of CX3CR1+CD8 T cells with aging and distinct clinical features in Sjögren's syndrome and IgG4-related disease.

机构信息

Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.

出版信息

Clin Exp Rheumatol. 2023 Dec;41(12):2409-2417. doi: 10.55563/clinexprheumatol/kfsd65. Epub 2023 Oct 5.

Abstract

OBJECTIVES

Recent studies have implicated cytotoxic CD4 and CD8 T cells in primary Sjögren's syndrome (pSS) and IgG4-related disease (IgG4-RD), but their association with immune aging and organ-specific clinical features remain unclear. CX3CR1 is expressed on cytotoxic CD4 and CD8 T cells. The aim of this study was to determine associations of peripheral CX3CR1+CD4 and CX3CR1+CD8 T cells with aging and clinical features.

METHODS

Whole blood samples were freshly obtained from consecutive patients with active, treatment-naïve pSS (n=57), IgG4-RD (n=54), and healthy individuals (n=40) and analysed by flow cytometry for CX3CR1+CD4 and CX3CR1+CD8 proportions. Associations of those T cells with aging and clinical features were determined.

RESULTS

CX3CR1+CD4 and CX3CR1+CD8 T cells selectively expressed perforin and granzyme B. Proportions of CX3CR1+CD4 and CX3CR1+CD8 T cells were significantly higher in pSS and IgG4-RD than in healthy individuals. Higher proportions of CX3CR1+CD8 T cells were associated with aging in pSS and IgG4-RD but not in healthy individuals. Sex differences were not associated with proportions of CX3CR1+CD8 T cells. Furthermore, patients with pSS with interstitial lung disease showed higher proportions of CX3CR1+CD8 T cells than those without interstitial lung disease. IgG4-RD patients with retroperitoneal fibrosis and/or aortitis exhibited higher proportions of CX3CR1+CD8 T cells compared with those with Mikulicz's disease. Moreover, proportions of CX3CR1+CD8 T cells were decreased following glucocorticoid treatment in paralleled with clinical improvements in IgG4-RD.

CONCLUSIONS

CX3CR1+CD8 T cells might be involved in immune aging and distinct clinical phenotypes of patients with pSS or IgG4-RD.

摘要

目的

最近的研究表明细胞毒性 CD4 和 CD8 T 细胞与原发性干燥综合征(pSS)和 IgG4 相关疾病(IgG4-RD)有关,但它们与免疫衰老和器官特异性临床特征的关系尚不清楚。CX3CR1 表达于细胞毒性 CD4 和 CD8 T 细胞上。本研究旨在确定外周血 CX3CR1+CD4 和 CX3CR1+CD8 T 细胞与衰老和临床特征的关系。

方法

连续采集活动期、未经治疗的 pSS(n=57)、IgG4-RD(n=54)患者和健康对照者(n=40)的新鲜全血样本,通过流式细胞术分析 CX3CR1+CD4 和 CX3CR1+CD8 比例。确定这些 T 细胞与衰老和临床特征的关系。

结果

CX3CR1+CD4 和 CX3CR1+CD8 T 细胞选择性表达穿孔素和颗粒酶 B。pSS 和 IgG4-RD 患者外周血 CX3CR1+CD4 和 CX3CR1+CD8 T 细胞比例明显高于健康对照者。pSS 和 IgG4-RD 患者中,CX3CR1+CD8 T 细胞比例与年龄相关,而健康对照者中则无此相关性。性别差异与 CX3CR1+CD8 T 细胞比例无关。此外,pSS 伴有间质性肺病患者的 CX3CR1+CD8 T 细胞比例高于无间质性肺病患者。伴有腹膜后纤维化和/或大动脉炎的 IgG4-RD 患者的 CX3CR1+CD8 T 细胞比例高于 Mikulicz 病患者。此外,IgG4-RD 患者经糖皮质激素治疗后,CX3CR1+CD8 T 细胞比例下降,临床症状改善。

结论

CX3CR1+CD8 T 细胞可能参与 pSS 或 IgG4-RD 患者的免疫衰老和不同的临床表型。

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