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.

中文翻译：

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转录因子 Foxp1 调节树突细胞的分化和功能

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起着关键作用。作为最强大的抗原呈递细胞，DC在维持免疫稳态和参与自身免疫性疾病的发展方面也很重要。DCs 的成熟和功能如何在这些条件下受到调节以及各种转录因子的功能是什么仍不清楚。在这项研究中，我们发现转录因子 Foxp1 的表达在 DCs 的成熟过程中逐渐增加。然后，我们构建了一种携带 Foxp1 干扰 RNA (Ad-simFoxp1) 的重组腺病毒，并在体外转染了小鼠骨髓来源的 DC。用 Ad-simFoxp1 转染的 DCs 表现出显着降低的共刺激分子和减少的细胞因子。Ad-simFoxp1 极大地抑制了成熟的 DC 诱导的 T 细胞反应。此外，体内输注 Ad-simFoxp1 修饰的 DCs 显着延迟了实验性自身免疫性脑脊髓炎 (EAE) 的发病。因此，在 DC 中过继转染 Ad-simFoxp1 可能是一种针对自身免疫性疾病的潜在治疗策略。