Unique glandular ex-vivo Th1 and Th17 receptor motifs in Sjögren's syndrome patients using single-cell analysis.
Unique glandular ex-vivo Th1 and Th17 receptor motifs in Sjögren's syndrome patients using single-cell analysis.
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DOI：
10.1016/j.clim.2018.04.009
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发表时间：
2018-07
期刊：
影响因子：
--
通讯作者：
Nguyen CQ
中科院分区：
文献类型：
--
作者：
Voigt A;Bohn K;Sukumaran S;Stewart CM;Bhattacharya I;Nguyen CQ
原发性Sjögren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通过单细胞分析确定pSS患者个体浸润T辅助细胞(Th)-1和17细胞的T细胞受体（TCR）谱。体外浸润T细胞的单细胞分析表明，pSS患者活化Th17细胞的频率更高。单细胞TCR测序结果显示，TCRβ变量（TRBV） 3-1 /joint (J) 1-2 （CLFLSMSACVW）和TRBV20-1 / J1-1 （SVGS-TAIPP*T）在两个队列中均由活化的Th1和Th17细胞表达。独特的是，TCRα变量（TRAV） 8-2 /J5 （VVSDTVLETAGE）仅在患者中存在的Th1细胞和Th1/Th17细胞中存在的互补决定区（CDR）3α特异性基元（LSTD*E）中表达。研究表明，pSS患者激活的Th1和Th17细胞均表现出有限的克隆多样性，其中在对照组和患者中存在两个CDR3基序，另外两个基序是pSS独有的。
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 (SVGS-TAIPP*T) 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 (LSTD*E) 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.
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