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共刺激受体信号淋巴细胞激活分子家族成员1(SLAMF1)在自身免疫性甲状腺炎患者淋巴细胞中的表达及功能改变

Expression and Function of the Costimulatory Receptor SLAMF1 Is Altered in Lymphocytes From Patients With Autoimmune Thyroiditis.

作者信息

Vitales-Noyola Marlen, Ramos-Levi Ana M, Serrano-Somavilla Ana, Martínez-Hernández Rebeca, Sampedro-Nuñez Miguel, Di Pasquale Carmelina, González-Amaro Roberto, Marazuela Mónica

机构信息

Department of Immunology, School of Medicine and.

Services of Endocrinology, Immunology and Molecular Biology Unit, Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, 28006 Madrid, Spain; and.

出版信息

J Clin Endocrinol Metab. 2017 Feb 1;102(2):672-680. doi: 10.1210/jc.2016-2322.

Abstract

CONTEXT

Signaling lymphocytic activation molecule family 1 (SLAMF1) is a costimulatory receptor expressed by most immune cells. Its role in autoimmune thyroid disease (AITD) is not well known.

OBJECTIVE

To analyze the expression and function of the costimulatory receptor SLAMF1 in lymphocytes of patients with AITD.

DESIGN

Cross-sectional, prospective, single-center study.

SETTING

Department of Endocrinology, Hospital Universitario de la Princesa, Madrid.

PATIENTS

Twenty-eight patients with AITD (17 with Graves disease and 11 with Hashimoto thyroiditis) and 21 controls.

INTERVENTION

Multiparametric flow cytometry and immunofluorescence techniques to analyze the expression of SLAMF1 in peripheral blood (n = 28) and thyroid tissue (n = 5) mononuclear cells. Assay of inhibition of cellular proliferation to study the function of SLAMF1 in CD4+CD25+ T regulatory (Treg) cells.

MAIN OUTCOME MEASURE

Expression levels and the function of SLAMF1 in lymphocytes in AITD patients and controls.

RESULTS

Expression of SLAMF1 was significantly increased in peripheral blood CD4+, T helper 17, and CD19+ B cells from AITD patients. Immunofluorescence microscopy detected the presence of SLAMF1+ lymphocytes in thyroid inflammatory cell infiltrate. Functional studies showed that SLAMF1 engagement in Treg cells increased their suppressive function in healthy controls but not in AITD patients.

CONCLUSIONS

The altered expression of SLAMF1, as well as its defective function observed in patients with AITD, may have a relevant role in the defective immune-regulatory function observed in this condition.

摘要

背景

信号淋巴细胞激活分子家族1(SLAMF1)是一种由大多数免疫细胞表达的共刺激受体。其在自身免疫性甲状腺疾病(AITD)中的作用尚不清楚。

目的

分析共刺激受体SLAMF1在AITD患者淋巴细胞中的表达及功能。

设计

横断面、前瞻性、单中心研究。

地点

马德里公主大学医院内分泌科。

患者

28例AITD患者(17例格雷夫斯病患者和11例桥本甲状腺炎患者)及21名对照者。

干预

采用多参数流式细胞术和免疫荧光技术分析外周血(n = 28)和甲状腺组织(n = 5)单个核细胞中SLAMF1的表达。通过细胞增殖抑制试验研究SLAMF1在CD4+CD25+调节性T(Treg)细胞中的功能。

主要观察指标

AITD患者和对照者淋巴细胞中SLAMF1的表达水平及功能。

结果

AITD患者外周血CD4+、辅助性T细胞17及CD19+B细胞中SLAMF1的表达显著增加。免疫荧光显微镜检查发现甲状腺炎性细胞浸润中有SLAMF1+淋巴细胞。功能研究表明,SLAMF1与Treg细胞结合可增强其在健康对照者中的抑制功能,但在AITD患者中无此作用。

结论

AITD患者中观察到的SLAMF1表达改变及其功能缺陷可能在该疾病中观察到的免疫调节功能缺陷中起重要作用。

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