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单细胞分析揭示干燥综合征患者独特的腺体外 Th1 和 Th17 受体基序。

Unique glandular ex-vivo Th1 and Th17 receptor motifs in Sjögren's syndrome patients using single-cell analysis.

机构信息

Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, Gainesville, Florida, USA.

Rheumatology Section, University of Arkansas for Medical Sciences, Arkansas Children's Hospital, Little Rock, Arkansas, USA.

出版信息

Clin Immunol. 2018 Jul;192:58-67. doi: 10.1016/j.clim.2018.04.009. Epub 2018 Apr 19.

Abstract

Primary Sjögren's syndrome (pSS) is an autoimmune disease in which the underlying cause has yet to be elucidated. The main objective of this study was to determine the T cell receptor (TCR) repertoires of individual infiltrating T helper (Th)-1 and 17 cells of pSS patients using single-cell analysis. Single-cell analysis of ex-vivo infiltrating T cells demonstrated that pSS patients had higher frequencies of activated Th17 cells. Single-cell TCR sequencing revealed that TCRβ variable (TRBV)3-1/joint (J)1-2 (CLFLSMSACVW) and TRBV20-1/J1-1 (SVGSTAIPPT) were expressed by activated Th1 and Th17 cells in both cohorts. Uniquely, TCRα variable (TRAV)8-2/J5 (VVSDTVLETAGE) was expressed by Th1 cells present only in patients and complementarity-determining region (CDR)3α-specific motif (LSTDE) present in both Th1/Th17 cells. The study demonstrates that both activated Th1 and Th17 cells of pSS patients showed restricted clonal diversities of which two CDR3 motifs were present in controls and patients, with another two motifs unique to pSS.

摘要

原发性干燥综合征(pSS)是一种自身免疫性疾病,其根本原因尚未阐明。本研究的主要目的是使用单细胞分析来确定 pSS 患者浸润性辅助性 T 细胞(Th)1 和 17 细胞的 T 细胞受体(TCR)谱。对体外浸润性 T 细胞的单细胞分析表明,pSS 患者激活的 Th17 细胞频率更高。单细胞 TCR 测序显示,在两个队列中,激活的 Th1 和 Th17 细胞均表达 TCRβ 可变(TRBV)3-1/联合(J)1-2(CLFLSMSACVW)和 TRBV20-1/J1-1(SVGSTAIPPT)。独特的是,仅在患者中存在的 Th1 细胞表达 TRAV8-2/J5(VVSDTVLETAGE),而在 Th1/Th17 细胞中均存在互补决定区(CDR)3α特异性基序(LSTDE)。该研究表明,pSS 患者的活化 Th1 和 Th17 细胞均表现出受限的克隆多样性,其中两个 CDR3 基序在对照组和患者中均存在,另外两个基序仅存在于 pSS 中。

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