Differentiation of follicular helper T cells by salivary gland epithelial cells in primary Sjogren's syndrome
Differentiation of follicular helper T cells by salivary gland epithelial cells in primary Sjogren's syndrome
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DOI：
10.1016/j.jaut.2013.11.003
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发表时间：
2014-06-01
影响因子：
12.8
通讯作者：
Gottenberg, Jacques-Eric
中科院分区：
文献类型：
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作者：
Gong, Ya-Zhuo;Nititham, Joanne;Gottenberg, Jacques-Eric
在淋巴结构中的B细胞活化和分化中起关键作用的滤泡辅助T细胞（Tfh）分泌IL-21，IL-21的分泌增强是几种自身免疫性疾病的标志。为了解释原发性干燥综合征（pSS）患者唾液腺中发生的细胞和分子相互作用，我们研究了唾液腺上皮细胞（SGEC）是否能够诱导Tfh分化。对pSS患者和对照组的初始CD 4（+）T细胞和SGEC进行共培养。在此，我们报道了SGEC表达IL-6和ICOSL有助于幼稚CD 4（+）T细胞分化为Tfh细胞，这一点可以通过它们获得特定的表型来证明，其特征在于Bcl-6、ICOS和CXCR 5表达和IL-21分泌，但也可以通过它们的主要功能功能：增强B淋巴细胞存活的能力来证明。我们证明了血清IL-21的增加具有全身活性。最后，我们分析了IL-21或IL-21 R基因多态性与pSS或IL-21分泌升高之间的潜在遗传关联。这项研究，这表明了直接诱导Tfh分化的SGECs，强调了一个未知的致病作用SGECs，并表明，Tfh和IL-21可能是相关的生物标志物和/或治疗靶点在原发性干燥综合征。(C)2013爱思唯尔有限公司保留所有权利。
Follicular helper T cells (Tfh), which play a pivotal role in B cell activation and differentiation in lymphoid structures, secrete IL-21 whose augmented secretion is a hallmark of several autoimmune diseases. To decipher the cellular and molecular interactions occurring in salivary glands of patients suffering from primary Sjogren's syndrome (pSS), we investigated whether salivary gland epithelial cells (SGECs) were capable to induce Tfh differentiation. Co-cultures of naive CD4(+) T cells and SGECs from both patients with pSS and controls were performed. Here, we report that IL-6 and ICOSL expression by SGECs contributes to naive CD4(+) T differentiation into Tfh cells, as evidenced by their acquisition of a specific phenotype, characterized by Bcl-6, ICOS and CXCR5 expression and IL-21 secretion, but also but by their main functional feature: the capacity to enhance B lymphocytes survival. We demonstrated an increase of serum IL-21 with systemic activity. Finally, we analyzed the potential occurrence of a genetic association between IL-21 or IL-21R gene polymorphisms and pSS or elevated IL-21 secretion. This study, which demonstrates a direct induction of Tfh differentiation by SGECs, emphasizes a yet unknown pathogenic role of SGECs and suggests that Tfh and IL-21 might be relevant biomarkers and/or therapeutic targets in primary Sjogren's syndrome. (C) 2013 Elsevier Ltd. All rights reserved.