转录因子Foxp1调节树突状细胞的分化和功能

IF 2.6 Q2 Medicine Mechanisms of Development Pub Date : 2019-08-01 DOI:10.1016/j.mod.2019.05.001
Ziyi Guo , Yijie Tao , Shulei Yin , Yuping Song , Xiaomin Lu , Xuesong Li , Yujuan Fan , Xiaofang Fan , Sheng Xu , Jialin Yang , Yizhi Yu
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引用次数: 2

摘要

树突状细胞(dc)是免疫系统的哨兵,在启动针对病原体的适应性免疫反应中发挥关键作用。作为最强大的抗原提呈细胞,树突状细胞在维持免疫稳态和参与自身免疫性疾病的发展中也很重要。在这些条件下,DCs的成熟和功能是如何调控的,各种转录因子的功能是什么,目前还不清楚。在本研究中,我们发现转录因子Foxp1的表达在树突状细胞成熟过程中逐渐增加。然后,我们构建了携带foxp1干扰RNA (Ad-simFoxp1)的重组腺病毒,并在体外转染小鼠骨髓源性dc。转染Ad-simFoxp1的树突状细胞显示出明显降低的共刺激分子和减少的细胞因子。Ad-simFoxp1极大地抑制成熟dc诱导的T细胞反应。此外,体内输注ad - simfoxp1修饰的dc可显著延缓实验性自身免疫性脑脊髓炎(EAE)的发作。因此,过继转染dc中的Ad-simFoxp1可能是一种潜在的治疗自身免疫性疾病的策略。
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The transcription factor Foxp1 regulates the differentiation and function of dendritic cells

Dendritic cells (DCs) are the sentinels of the immune system and play a critical role in initiating adaptive immune responses against pathogens. As the most powerful antigen presenting cells, DCs are also important in maintaining immune homeostasis and participating in the development of autoimmune diseases. How the maturation and function of DCs is regulated in these conditions and what is the function of various transcription factors is still unclear. In this study, we found that the expression of the transcription factor Foxp1 gradually increased during the maturation of DCs. Then, we constructed a recombinant adenovirus carrying Foxp1-interfering RNA (Ad-simFoxp1) and transfected murine bone marrow-derived DCs in vitro. DCs transfected with Ad-simFoxp1 exhibited markedly lower costimulatory molecules, and decreased cytokines. And Ad-simFoxp1 greatly inhibited mature DC-induced T cell responses. Moreover, in vivo infusion with Ad-simFoxp1-modified DCs significantly delayed the onset of experimental autoimmune encephalomyelitis (EAE). Therefore, adoptive transfection of Ad-simFoxp1 in DCs may be a potential treatment strategy against autoimmune diseases.

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来源期刊
Mechanisms of Development
Mechanisms of Development 生物-发育生物学
CiteScore
3.60
自引率
0.00%
发文量
0
审稿时长
12.4 weeks
期刊介绍: Mechanisms of Development is an international journal covering the areas of cell biology and developmental biology. In addition to publishing work at the interphase of these two disciplines, we also publish work that is purely cell biology as well as classical developmental biology. Mechanisms of Development will consider papers in any area of cell biology or developmental biology, in any model system like animals and plants, using a variety of approaches, such as cellular, biomechanical, molecular, quantitative, computational and theoretical biology. Areas of particular interest include: Cell and tissue morphogenesis Cell adhesion and migration Cell shape and polarity Biomechanics Theoretical modelling of cell and developmental biology Quantitative biology Stem cell biology Cell differentiation Cell proliferation and cell death Evo-Devo Membrane traffic Metabolic regulation Organ and organoid development Regeneration Mechanisms of Development does not publish descriptive studies of gene expression patterns and molecular screens; for submission of such studies see Gene Expression Patterns.
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