To elucidate the effect of macrophages on human neurons, we used a co-culture system of control human-induced pluripotent stem cell-derived neurons and differentiated macrophages obtained from the peripheral blood mononuclear cells of five TD individuals and five individuals with ASD. All participants were male and ethnically Japanese.
Our results of co-culture experiments showed that GM-CSF MΦ affect the dendritic outgrowth of neurons through the secretion of pro-inflammatory cytokines, interleukin-1α and TNF-α. Macrophages derived from individuals with ASD exerted more severe effects than those derived from TD individuals.
The main limitations of our study were the small sample size with a gender bias toward males, the use of artificially polarized macrophages, and the inability to directly observe the interaction between neurons and macrophages from the same individuals.
Our co-culture system revealed the non-cell autonomous adverse effects of GM-CSF MΦ in individuals with ASD on neurons, mediated by interleukin-1α and TNF-α. These results may support the immune dysfunction hypothesis of ASD, providing new insights into its pathology.
方法:为了阐明巨噬细胞对人类神经元的影响,我们使用的共培养系统包括控制人诱导多能干细胞来源的神经元和从5名TD个体和5名ASD个体的外周血单核细胞中获得的分化巨噬细胞。所有参与者都是男性和日本种族。
结果:我们的共培养实验结果表明,GM-CSFMΦ通过分泌促炎细胞因子影响神经元的树突生长,白细胞介素-1α和TNF-α。来自ASD个体的巨噬细胞比来自TD个体的巨噬细胞产生更严重的影响。
结论:我们研究的主要局限性是样本量小,对男性有性别偏见,使用人工极化的巨噬细胞,并且无法直接观察来自同一个体的神经元和巨噬细胞之间的相互作用。
结论:我们的共培养系统揭示了GM-CSFMΦ在ASD患者中对神经元的非细胞自主不良反应,由白细胞介素-1α和TNF-α介导。这些结果可能支持ASD的免疫功能障碍假说。提供对其病理学的新见解。