The transcription factor Foxp1 regulates the differentiation and function of dendritic cells
The transcription factor Foxp1 regulates the differentiation and function of dendritic cells
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转录因子Foxp1调节树突状细胞的分化和功能
DOI：
10.1016/j.mod.2019.05.001
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发表时间：
2019-08-01
影响因子：
2.6
通讯作者：
Yu, Yizhi
中科院分区：
文献类型：
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作者：
Guo, Ziyi;Tao, Yijie;Yu, Yizhi
树突状细胞（Dendritic cells，DCs）是免疫系统的哨兵，在启动针对病原体的适应性免疫应答中起着关键作用。作为功能最强的抗原提呈细胞，DC在维持免疫稳态和参与自身免疫性疾病的发生发展中也起着重要作用。在这些条件下如何调节DC的成熟和功能以及各种转录因子的功能仍然不清楚。在本研究中，我们发现转录因子Foxp 1的表达在DC成熟过程中逐渐增加。然后，构建携带Foxp 1干扰RNA的重组腺病毒（Ad-simFoxp 1），体外转染小鼠骨髓来源的DC。转染Ad-simFoxp 1的DC表现出明显降低的共刺激分子，并减少细胞因子。Ad-simFoxp 1对DC诱导的T细胞应答有明显的抑制作用。此外，在体内输注Ad-simFoxp 1修饰的DC显着延迟实验性自身免疫性脑脊髓炎（EAE）的发病。因此，Ad-simFoxp 1过继转染DCs可能是一种潜在的治疗自身免疫性疾病的策略。
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.