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Modulation of the function of dendritic cells in adolescents with chronic HBV infection by IFN-λ1

机译:IFN-λ1对慢性HBV感染青少年树突细胞功能的调节

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摘要

The exact immunology pathogenesis of hepatitis B virus (HBV) infection remains unclear currently. The dendritic cells (DCs) dysfunction is evident in adolescents with chronic HBV infection in the immune tolerant phase. DCs, as the most efficient professional antigen-presenting cells (APCs), possess the strongest antigen presenting the effect in the body and can stimulate the initial T cell activation and proliferation, depending on their stage of maturation. The recently classified type III interferon group, interferon-λ1 (IL-29), interferon-λ2 (IL-28A), and interferon-λ3 (IL-28B) displays immunomodulatory and antiviral activity. In the current study, we describe a way to stimulate the DCs maturation. As a result, IFN-λ1 combined with recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) and recombinant human interleukin-4 (rhIL-4) can induce the DCs maturation and promote the costimulatory molecules such as CD80, CD83, CD86 and human leucocyte antigen DR (HLA-DR) expression in the immune tolerance and the clearance phases. This study demonstrates that the DCs function is remarkably impaired both in the immune tolerant phase and the immune clearance phase in adolescents with chronic HBV infection compared with healthy youth control. At the same time, this study has developed a theoretical basis for the application of IFN-λ1 breaking immune tolerance and improving the body’s immune system to clear HBV.
机译:目前尚不清楚乙型肝炎病毒(HBV)感染的确切免疫学发病机制。树突状细胞(DCs)功能障碍在免疫耐受期慢性HBV感染的青少年中很明显。 DC作为最有效的专业抗原呈递细胞(APC),在体内具有最强的抗原呈递作用,并可以根据其成熟阶段刺激最初的T细胞活化和增殖。最近分类的III型干扰素组,干扰素λ1(IL-29),干扰素λ2(IL-28A)和干扰素λ3(IL-28B)显示免疫调节和抗病毒活性。在当前的研究中,我们描述了一种刺激DC成熟的方法。结果,IFN-λ1与重组人粒细胞-巨噬细胞集落刺激因子(rhGM-CSF)和重组人白细胞介素-4(rhIL-4)结合可诱导DC成熟并促进共刺激分子,例如CD80,CD83,CD86和人类白细胞抗原DR(HLA-DR)在免疫耐受和清除阶段的表达。这项研究表明,与健康的青年对照组相比,慢性HBV感染青少年的DCs功能在免疫耐受期和免疫清除期均显着受损。同时,这项研究为应用IFN-λ1打破免疫耐受并改善人体免疫系统清除HBV奠定了理论基础。

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