干燥综合症患者唾液腺上皮细胞促进了滤泡辅助性T细胞的分化
发表者：杨霖
日期：2015-02-27
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摘要 目的：滤泡辅助性T细胞（Tfh）在B细胞的活化和分化起到了举足轻重的作用，而IL- 21的分泌增强则是几种自身免疫性疾病的一个重要标志。为了进一步了解干燥综合症患者唾液腺受累的细胞和分子间的机制，我们研究了唾液腺上皮细胞（SGECs）是否能够诱导分化Tfh细胞。
方法：研究者通过共培养来自患者的早期CD4和唾液腺上皮细胞来进行这个研究。流式细胞术分析Tfh的表面标志物及IL-21的表达，同时分析了患者体内IL-21基因与疾病的相关性
结果：显示SGECs的IL-6和ICOSL表达有助于早期CD4T细胞分化为Tfh细胞，Tfh细胞特定表型是BCL-6，ICOS和CXCR5表达和IL- 21的表达，并且能够增强B淋巴细胞的生存能力。同时，研究者发现血清中IL- 21与疾病的活动度密切相关。研究者最后分析了IL-21和IL -21R基因多态性和原发性干燥综合症患者IL-21的分泌之间的相关性，结果发现IL-21和IL -21R基因多态性与疾病并无相关性。
结论：该研究成果提示SGECs直接诱导Tfh产生和分化，说明了SGECs发挥了一个潜在致病的角色，而Tfh和IL-21可作为原发性干燥综合征相关生物标志物和/或治疗靶点。
附原文：Abstract：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 Sjögren's syndrome (pSS), we investigated whether salivary gland epithelial cells (SGECs) were capable to induce Tfh differentiation. Co-cultures of naïve 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 naïve 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 Sjögren's syndrome.
引自：Gong YZ, Nititham J, Taylor K, Miceli-Richard C, Sordet C, Wachsmann D, Bahram S, Georgel P, Criswell LA, Sibilia J, Mariette X, Alsaleh G, Gottenberg JE. Differentiation of follicular helper T cells by salivary gland epithelial cells in primary Sjögren's syndrome. J Autoimmun. 2014 Jan 9. pii: S0896-8411(13)00147-9. doi: 10.1016/j.jaut.2013.11.003. （注：干燥综合症病人或亲属可加QQ群交流，群号： 118194945 ，本网站站长私人微信号： ssgzz88 ）
方法：研究者通过共培养来自患者的早期CD4和唾液腺上皮细胞来进行这个研究。流式细胞术分析Tfh的表面标志物及IL-21的表达，同时分析了患者体内IL-21基因与疾病的相关性
结果：显示SGECs的IL-6和ICOSL表达有助于早期CD4T细胞分化为Tfh细胞，Tfh细胞特定表型是BCL-6，ICOS和CXCR5表达和IL- 21的表达，并且能够增强B淋巴细胞的生存能力。同时，研究者发现血清中IL- 21与疾病的活动度密切相关。研究者最后分析了IL-21和IL -21R基因多态性和原发性干燥综合症患者IL-21的分泌之间的相关性，结果发现IL-21和IL -21R基因多态性与疾病并无相关性。
结论：该研究成果提示SGECs直接诱导Tfh产生和分化，说明了SGECs发挥了一个潜在致病的角色，而Tfh和IL-21可作为原发性干燥综合征相关生物标志物和/或治疗靶点。
附原文：Abstract：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 Sjögren's syndrome (pSS), we investigated whether salivary gland epithelial cells (SGECs) were capable to induce Tfh differentiation. Co-cultures of naïve 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 naïve 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 Sjögren's syndrome.
引自：Gong YZ, Nititham J, Taylor K, Miceli-Richard C, Sordet C, Wachsmann D, Bahram S, Georgel P, Criswell LA, Sibilia J, Mariette X, Alsaleh G, Gottenberg JE. Differentiation of follicular helper T cells by salivary gland epithelial cells in primary Sjögren's syndrome. J Autoimmun. 2014 Jan 9. pii: S0896-8411(13)00147-9. doi: 10.1016/j.jaut.2013.11.003. （注：干燥综合症病人或亲属可加QQ群交流，群号： 118194945 ，本网站站长私人微信号： ssgzz88 ）