Direct infection of primary salivary gland epithelial cells by HTLV-I that induces the niche of the salivary glands of Sjögren’s syndrome patients.
Direct infection of primary salivary gland epithelial cells by HTLV-I that induces the niche of the salivary glands of Sjögren’s syndrome patients.
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HTLV-I 直接感染原代唾液腺上皮细胞，诱导干燥综合征患者唾液腺微环境的形成。
DOI：
10.1002/art.39009
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Kawakami A.
中科院分区：
文献类型：
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作者：
Nakamura H;Takahashi Y;Yamamoto-Fukuda T;Horai Y;Nakashima Y;Arima K;Nakamura T;Koji T;Kawakami A.
目的探讨人类嗜T淋巴细胞病毒I型(HTLV-I)感染干燥综合征(SS)患者唾液腺上皮细胞(SGECs)是否直接感染SGECs并诱导涎腺小窝的形成。用抗体阵列、免疫荧光分析和酶联免疫吸附试验(ELISA)检测炎症相关分子的表达谱，用抗体阵列和免疫荧光分析检测细胞凋亡相关分子的表达谱。免疫荧光分析和原位聚合酶链式反应检测HTLV-I相关分子的存在。结果与HCT-5细胞共同培养96h后，SGECs中HTLV-I相关蛋白阳性率为7.8±1.3%(平均值±SD)。核转录因子κB p65在10%的SGEC中也有表达。用原位聚合酶链式反应检测与HCT-5细胞共培养后SGECs中HTLV-I前病毒DNA的存在。与Hct-5共培养后，细胞因子和趋化因子，包括可溶性细胞间黏附分子1、RANTES和干扰素γ诱导蛋白10kd(IP-10/CXCL10)的表达呈时间依赖性增加。在与HCT-5共同培养的SGECs中，促凋亡分子(如细胞色素c和Fas)和抗凋亡分子(如Bcl2、Hsp27)的表达增加，表明与HCT-5或Jurkat细胞共同培养后，SGECs未检测到凋亡。结论HTLV-I感染SGECs并改变其细胞功能。这些变化可能诱导了SS的生态位，并有助于抗HTLV-I抗体阳性个体SS的发生。
ObjectiveTo investigate whether human T lymphotropic virus type I (HTLV‐I) directly infects salivary gland epithelial cells (SGECs) and induces the niche of the salivary glands in patients with Sjögren's syndrome (SS).MethodsSGECs were cultured with the HTLV‐I–producing CD4+ T cell line HCT‐5 or with Jurkat cells. Antibody arrays, immunofluorescence analysis, and enzyme‐linked immunosorbent assay (ELISA) were used to determine the profiles of inflammation‐related molecules, and the profiles of apoptosis‐related molecules were determined by antibody array and immunofluorescence analysis. The presence of HTLV‐I–related molecules was assessed by immunofluorescence analysis and in situ polymerase chain reaction. Apoptosis of SGECs was evaluated by TUNEL staining.ResultsAmong the SGECs, 7.8 ± 1.3% (mean ± SD) were positive for HTLV‐I–related proteins after 96‐hour coculture with HCT‐5 cells. Nuclear NF‐κB p65 was also detected in 10% of the SGECs. The presence of HTLV‐I proviral DNA in SGECs after coculture with HCT‐5 cells was detected by in situ polymerase chain reaction. After coculture of SGECs with HCT‐5, the expression of cytokines and chemokines, including soluble intercellular adhesion molecule 1, RANTES, and interferon γ–induced protein 10 kd (IP‐10/CXCL10) was increased in a time‐dependent manner. The expression of proapoptotic molecules (e.g., cytochrome c and Fas) and antiapoptotic molecules (e.g., Bcl‐2, Heme oxygenase 2, and Hsp27) was increased in the SGECs cocultured with HCT‐5, showing that apoptosis of SGECs was not detected after coculture with HCT‐5 or Jurkat cells.ConclusionHTLV‐I is thought to infect SGECs and alter their cellular functions. These changes may induce the niche of SS and contribute to the development of SS in anti–HTLV‐I antibody–positive individuals.