Single cell transcriptomic studies of an Antigen-Specific Dual Microparticle Treatment of a Mouse Model of Multiple Sclerosis

A microparticle system using GMCSF, TGF-b, and VD3 along with disease specific antigen (Myelin Oligodendrocyte Protein) shows effiacy in treating a mouse model of multiple sclerosis, while GMCSF, TGF-b, and VD3 and irrelevant OVA antigen did not reduce scores. Here we show that pro-inflammatory and cell cycle genes are downregulated in multiple populations. scRNA-seq further revealed a reduction in antigen-presentation gene signature. One pair of mice was from the spinal cord and two mice from the ingunial lymph nodes. Mice treated with an antigen-specific microparticle system were compared to mice treated with an irrelevant antigen. Results compared OVA and MOG in the CNS and OVA vs. MOG in the lymph node separately.

本研究中，联合粒细胞-巨噬细胞集落刺激因子（Granulocyte-Macrophage Colony-Stimulating Factor，GMCSF）、转化生长因子-β（Transforming Growth Factor-β，TGF-β）与维生素D3（Vitamin D3，VD3），并搭载疾病特异性抗原髓鞘少突胶质细胞蛋白（Myelin Oligodendrocyte Protein，MOG）的微粒系统，在多发性硬化症小鼠模型中展现出明确的治疗效果；而仅搭载GMCSF、TGF-β、VD3与无关抗原卵清蛋白（Ovalbumin，OVA）的微粒系统，则未能降低疾病评分。
本研究证实，多个细胞群中的促炎基因与细胞周期基因均出现表达下调。单细胞RNA测序（single-cell RNA sequencing，scRNA-seq）进一步揭示，抗原呈递基因特征的表达水平显著降低。
本次实验纳入的小鼠样本中，2只取材自脊髓，2只取材自腹股沟淋巴结。将接受抗原特异性微粒系统处理的小鼠与接受无关抗原微粒系统处理的小鼠进行对照，实验分别针对中枢神经系统（Central Nervous System，CNS）内的OVA与MOG、以及淋巴结内的OVA与MOG的结果进行了独立比较分析。