Selective localization of T helper subsets in labial salivary glands from primary Sjögren's syndrome patients.

Selective localization of T helper subsets in labial salivary glands from primary Sjögren's syndrome patients.
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DOI:
10.1111/j.1365-2249.2012.04606.x
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发表时间:
2012-08
影响因子:
4.6
通讯作者:
Nakamura S
Nakamura S
中科院分区:
医学3区
文献类型:
--
作者:
Maehara T;Moriyama M;Hayashida JN;Tanaka A;Shinozaki S;Kubo Y;Matsumura K;Nakamura S

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本研究的目的是通过检测辅助性T细胞(Th1, Th2, Th17调节性T细胞(Tregs)和滤泡辅助性T细胞(Tfh)的选择性定位,研究原发性Sjögren综合征(SS)患者唇唾液腺(LSGs)病变自身免疫损伤的开始和进展。使用实时聚合酶链反应(PCR)和免疫染色检测54例SS患者和16例健康对照的LSGs中与这些Th亚群相关的细胞因子和转录因子的表达。采用激光捕获显微解剖(LCM)的方法,选择性地提取了8例SS患者LSGs标本中无生发中心(GC-)和有生发中心(GC+)的浸润淋巴细胞。通过实时荧光定量PCR比较GC-和GC+两组样品中这些分子的mRNA表达情况。与对照组相比,SS患者LSGs中所有辅助性T (Th)亚群的细胞因子和转录因子的mRNA表达均显著升高。在SS患者的LSGs中,Th2和Tfh与强淋巴细胞浸润密切相关;而Th1、Th17和Tregs则没有。在选择性提取的LSGs病变中,GC-中检测到Th1和th17相关分子,GC+中检测到Th2和tfh相关分子。相比之下,treg相关分子与强淋巴细胞浸润无显著关联。这些结果表明SS在LSGs中有Th1、Th2、Th17和Tfh等Th亚群的选择性定位,这与疾病的严重程度和/或状态密切相关。SS可能由Th1和Th17细胞启动,然后由Th2和Tfh细胞通过GC形成进行进展。
The aim of this study was to investigate the initiation and progression of autoimmune damage in the lesions of labial salivary glands (LSGs) from primary Sjögren's syndrome (SS) patients by examining the selective localization of T helper (Th) subsets such as Th1, Th2, Th17 regulatory T cells (Tregs) and follicular T helper cells (Tfh). The expression of cytokines and transcription factors associated with these Th subsets in the LSGs from 54 SS patients and 16 healthy controls was examined using real-time polymerase chain reaction (PCR) and immunostaining. Additionally, infiltrating lymphocytes without germinal centre (GC-) and with GC (GC+) in the LSGs specimens from eight SS patients were extracted selectively by laser capture microdissection (LCM). The mRNA expression of these molecules was compared between the two sample groups of GC- and GC+ by real-time PCR. The mRNA expression of cytokines and transcription factors of all T helper (Th) subsets in the LSGs from the SS patients was increased significantly in comparison with controls. In LSGs from the SS patients, Th2 and Tfh was associated closely with strong lymphocytic infiltration; however, Th1, Th17 and Tregs was not. In the selectively extracted lesions of LSGs, Th1 and Th17-related molecules were detected strongly in the GC-, while Th2 and Tfh-related molecules were detected in the GC+. In contrast, no significant association with strong lymphocytic infiltration was observed in Treg-related molecules. These results indicate that SS has selective localization of Th subsets such as Th1, Th2, Th17 and Tfh in the LSGs, which is associated closely with disease severity and/or status. SS might be initiated by Th1 and Th17 cells, and then progressed by Th2 and Tfh cells via GC formation.
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