J Adv Res|中山大学第三附属医院江滢团队指明转录因子NFIL3可调节不同免疫细胞亚群以缓解EAE

2022年8月4日 0条评论 495次阅读 0人点赞

最新细胞功能及机制文献分享

以往的研究表明，转录因子NFIL3可对免疫系统发挥综合作用，其与不同免疫细胞亚群的功能和发育有关。实验性自身免疫性脑脊髓炎（EAE）由免疫细胞介导，可导致中枢神经系统（CNS）中的炎性脱髓鞘。然而，NFIL3如何影响EAE尚未得到彻底研究。2021年11月14日，中山大学第三附属医院神经内科江滢团队在Journal of Advanced Research上发表了题为“NFIL3 deficiency alleviates EAE through regulating different immune cell subsets”的研究论文。在本研究中，团队旨在研究NFIL3如何影响EAE，尤其是T细胞和树突状细胞的变化以及它们之间的相互作用。团队通过采用NFIL3^-/-小鼠和C57BL/6J小鼠（野生型）来建立MOG35-55诱导EAE模型，并每日记录临床评分。在体内模型的基础上，团队还通过流式细胞术分析了EAE小鼠中枢神经系统内外的免疫细胞，以及组织学方法评估中枢神经系统的神经炎症和脱髓鞘。体外通过CD11c⁺树突状细胞（DC）与T细胞的共培养实验检测了相互作用。结果证明，NFIL3通过调节不同免疫细胞亚群参与MOG35-55诱导的EAE，不仅与适应性免疫和先天免疫有关，还与它们之间的相互作用相关，尤其是CD4⁺T细胞和CD11c⁺树突细胞。

多发性硬化症（MS）是一种自身免疫性疾病，EAE是一种广泛用于研究MS的动物模型。根据之前的研究，自身反应性T细胞，尤其是Th1细胞（IFN-γ⁺）、Th17细胞（IL-17⁺）和调节性T细胞（Tregs），在MS与EAE的发病机制中很重要。此外，先天免疫细胞，如树突状细胞，也参与其中。NFIL3是哺乳动物碱性亮氨酸拉链转录因子之一，与许多生理生化过程有关，涉及调节生物钟、神经元生长和存活，可在先天免疫和适应性免疫中发挥综合作用。

基于此，团队假设NFIL3可能以不同的方式调节EAE。为验证猜想，研究团队通过系列体内外实验证明，NFIL3敲除EAE小鼠CNS内的Th17细胞显著减少，并伴随着较低的临床评分和较轻的神经炎症以及脱髓鞘；而在CNS之外，CD4⁺T细胞上的PD-1和ICOS显著增加，但Th2、Th9、CD8⁺CD103⁺T细胞以及GM-CSF⁺CD4⁺T细胞却显著减少；此外，NFIL3^-/-CD11c⁺树突状细胞的促炎能力受损，而抗炎能力得到提升。综上所述，研究团队提出NFIL3可通过调节先天性和适应性免疫以及它们之间的相互作用（尤其是DC细胞和T细胞）来缓解MOG_35-55诱导的EAE；敲除NFIL3会抑制T细胞向CNS的募集，最终缓解EAE神经功能障碍。

《J Adv Res|中山大学第三附属医院江滢团队指明转录因子NFIL3可调节不同免疫细胞亚群以缓解EAE》

图本文图形摘要示意图。

期刊及DOI号

J Adv Res. 2021 Nov 14.

doi: 10.1016/j.jare.2021.10.011.

题目

NFIL3 deficiency alleviates EAE through regulating different immune cell subsets

摘要

背景：The transcription factor NFIL3 exerts comprehensive effects on the immune system. Previous studies revealed that NFIL3 is related to the function and development of different immune cell subsets. Experimental autoimmune encephalomyelitis (EAE) is mediated by immune cells which results in inflammatory demyelination in the central nervous system (CNS). However, how NFIL3 affects EAE has not been thoroughly studied.

目标：The current study aimed to investigate how NFIL3 affects EAE, especially the changes of T cells and dendritic cells as well as the crosstalk between them.

方法：We used NFIL3^-/- mice and C57BL/6J mice (wildtype) to establish MOG35-55-induced EAE. The clinical scores were recorded daily. The immune cells within and outside the CNS of EAE mice were analyzed by flow cytometry. Histology was used to evaluated the neuroinflammation and demyelination in the CNS. Besides, CD11c⁺ dendritic cells (DCs) were cocultured with T cells and the interplay was measured.

结果：At the peak of EAE, Th17 cells decreased within the CNS accompanying with lower clinical scores and milder neuroinflammation and demyelination in NFIL3 knockout EAE mice. Outside the CNS, PD-1 and ICOS on CD4⁺T cells increased, whereas Th2, Th9, CD8⁺CD103⁺T cells and GM-CSF⁺CD4⁺T cells decreased. Besides, the pro-inflammatory capacity of NFIL3^-/-CD11c⁺ dendritic cells was impaired while the anti-inflammatory capacity was promoted.

结论：This study suggests that NFIL3 deficiency could alleviate MOG35-55-induced EAE through regulating different immune cell subsets, which is not only related with adaptive immunity and innate immunity, but also related with the cross-talk between them, especially CD4⁺T cells and CD11c⁺ dendritic cells.