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Thyrocyte-derived exosome-targeted dendritic cells stimulate strong CD4(+) T lymphocyte responses

机译:甲状腺细胞衍生的外侧靶向树突细胞刺激强CD4(+)T淋巴细胞反应

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摘要

Exosomes have been intensively studied in autoimmune diseases, and circulating exosomes and microvesicles have also been explored in autoimmune thyroiditis (AITD). However, the role of thyroid cell-derived exosomes in immune responses is unclear. We showed that IFN-gamma-treated Nthy-ori 3-1 cell-derived exosomes (IFN-gamma-Exo) harbored TPO, HSP60 and MHC-II and activated dendritic cells (DCs) in vitro. Compared with Exo-targeted DCs (DCExo), IFN-gamma-Exo-targeted DCs (DCIFN-gamma-Exo) promoted the expression and release of proinflammatory cytokines, such as IFN-gamma, IL-17A and IL-22, from CD4(+) T lymphocytes and inhibited the expression and release of antiinflammatory cytokines, such as IL-4, IL-10 and TGF-beta 1; however, IFN-gamma-Exo did not have this effect compared with Nthy-ori 3-1 cell-derived exosomes (Exo). DCIFN-gamma-Exo stimulates the expression and release of cytokines from CD4(+) T lymphocytes more efficiently than FN-gamma-Exo. Thus, DC(IFN-gamma-Exo )may effectively induce CD4(+) T lymphocyte-mediated immune responses and play a role in the occurrence and development of AITD.
机译:在自身免疫性疾病中,外泌体已经深入研究,并且还在自身免疫甲状腺炎(AITD)中探讨了循环外泌体和微铅。然而,甲状腺细胞衍生的外泌体在免疫应答中的作用尚不清楚。我们展示IFN-Gamma治疗的NThy-ORI 3-1细胞衍生的外泌体(IFN-Gamma-EXO)覆盖TPO,HSP60和MHC-II和体外活化的树突细胞(DCS)。与EXO靶向DCS(DCEXO)相比,IFN-GAMMA-EXO靶向DC(DCIFN-GAMMA-EXO)促进了促炎细胞因子的表达和释放,例如IFN-GAMMA,IL-17A和IL-22,来自CD4 (+)T淋巴细胞并抑制抗炎细胞因子的表达和释放,例如IL-4,IL-10和TGF-β1;然而,与Nthy-ORI 3-1细胞衍生的外泌体(EXO)相比,IFN-Gamma-EXO没有这种效果。 DCIFN-Gamma-EXO比FN-Gamma-EXO更有效地刺激CD4(+)T淋巴细胞的细胞因子的表达和释放。因此,DC(IFN-Gamma-EXO)可以有效地诱导CD4(+)T淋巴细胞介导的免疫反应,并在AITD的发生和发展中发挥作用。

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