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半乳糖凝集素-7 通过抑制 TGFβ/Smad3 通路促进激活的 CD4+T 细胞增殖和向 Th1/2 细胞向 Th1 的极化。

Galectin-7 promotes proliferation and Th1/2 cells polarization toward Th1 in activated CD4+ T cells by inhibiting The TGFβ/Smad3 pathway.

机构信息

Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.

Department of Anesthesiology and Critical Care, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.

出版信息

Mol Immunol. 2018 Sep;101:80-85. doi: 10.1016/j.molimm.2018.06.003. Epub 2018 Jun 8.

DOI:10.1016/j.molimm.2018.06.003
PMID:29890367
Abstract

Galectin-7 (Gal-7) has been associated with cell proliferation and apoptosis. It is known that Gal-7 antagonises TGFβ-mediated effects in hepatocytes by interacting with Smad3. Previously, we have demonstrated that Gal-7 is related to CD4+ T cells responses; nevertheless, its effect and functional mechanism on CD4+ T cells responses remain unclear. The murine CD4+ T cells were respectively cultured with Gal-7, anti-CD3/CD28 mAbs, or with anti-CD3/CD28 mAbs & Gal-7. The effects of Gal-7 on proliferation and the phenotypic changes in CD4+ T cells were assessed by flow cytometry. The cytokines from CD4+ T cells were analysed by quantitative real-time PCR. Subcellular localisation and expression of Smad3 were determined by immunofluorescence staining and Western blot, respectively. Gal-7 enhanced the proliferation of activated CD4+ T cells in a dose- and β-galactoside-dependent manner. Additionally, Gal-7 treatment did not change the ratio of Th2 cells in activated CD4+ T cells, while it increased the ratio of Th1 cells. Gal-7 also induced activated CD4+ T cells to produce a higher level of IFN-γ and TNF-α and a lower level of IL-10. Moreover, Gal-7 treatment significantly accelerated nuclear export of Smad3 in activated CD4+ T cells. These results revealed a novel role of Gal-7 in promoting proliferation and Th1/2 cells polarization toward Th1 in activated CD4+ T cells by inhibiting the TGFβ/Smad3 pathway.

摘要

半乳糖凝集素-7(Gal-7)与细胞增殖和凋亡有关。已知 Gal-7 通过与 Smad3 相互作用拮抗 TGFβ 在肝细胞中的作用。以前,我们已经证明 Gal-7 与 CD4+T 细胞反应有关;然而,其对 CD4+T 细胞反应的影响及其功能机制尚不清楚。将鼠 CD4+T 细胞分别用 Gal-7、抗 CD3/CD28 mAb 或抗 CD3/CD28 mAb 和 Gal-7 培养。通过流式细胞术评估 Gal-7 对 CD4+T 细胞增殖和表型变化的影响。通过定量实时 PCR 分析 CD4+T 细胞中的细胞因子。通过免疫荧光染色和 Western blot 分别确定 Smad3 的亚细胞定位和表达。Gal-7 以剂量和β-半乳糖苷依赖性方式增强活化的 CD4+T 细胞的增殖。此外,Gal-7 处理不会改变活化的 CD4+T 细胞中 Th2 细胞的比例,而增加 Th1 细胞的比例。Gal-7 还诱导活化的 CD4+T 细胞产生更高水平的 IFN-γ和 TNF-α和更低水平的 IL-10。此外,Gal-7 处理显著加速了活化的 CD4+T 细胞中 Smad3 的核输出。这些结果揭示了 Gal-7 通过抑制 TGFβ/Smad3 途径在促进活化的 CD4+T 细胞增殖和 Th1/2 细胞向 Th1 极化中的新作用。

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