Disease-specific oligodendrocyte lineage cells arise in multiple sclerosis.
Disease-specific oligodendrocyte lineage cells arise in multiple sclerosis.
复制标题
DOI：
10.1038/s41591-018-0236-y
复制
发表时间：
2018-12
期刊：
影响因子：
82.9
通讯作者：
Castelo-Branco G
中科院分区：
文献类型：
--
作者：
Falcão AM;van Bruggen D;Marques S;Meijer M;Jäkel S;Agirre E;Samudyata;Floriddia EM;Vanichkina DP;Ffrench-Constant C;Williams A;Guerreiro-Cacais AO;Castelo-Branco G
多发性硬化症（MS）的特征在于针对髓鞘的免疫系统攻击，髓鞘由少突胶质细胞（OL）产生。我们进行了单细胞转录组学分析OL谱系细胞从脊髓诱导的小鼠实验性自身免疫性脑脊髓炎（EAE），模拟MS的几个方面。我们发现独特的OL和OL前体细胞（OPC）在EAE和发现几个基因特异性地选择性剪接在这些细胞。令人惊讶的是，EAE特异性OL谱系群体表达的基因参与抗原加工和呈递通过主要组织相容性复合体I类和II类（MHC-I和-II），并在免疫保护，这表明这些细胞在疾病背景下的替代功能。重要的是，我们发现疾病特异性少突胶质细胞也存在于人类MS大脑中，并且大量已知为MS易感基因的基因（迄今为止主要与免疫细胞相关）在OL谱系细胞中表达。最后，我们证明了OPCs可以吞噬，表达MHC-II的OPCs可以激活记忆和效应CD 4 + T细胞。我们的研究结果表明，OLs和OPCs不是被动的目标，而是主动的免疫调节剂在MS的疾病特异性OL谱系细胞，我们确定了几个生物标志物，可能代表免疫调节治疗方法在MS的新的直接目标。
Multiple Sclerosis (MS) is characterised by an immune system attack targeting myelin, which is produced by oligodendrocytes (OLs). We performed single-cell transcriptomic analysis of OL lineage cells from the spinal cord of mice induced with experimental autoimmune encephalomyelitis (EAE), which mimics several aspects of MS. We found unique OLs and OL precursor cells (OPCs) in EAE and uncovered several genes specifically alternatively spliced in these cells. Surprisingly, EAE-specific OL-lineage populations expressed genes involved in antigen processing and presentation via major histocompatibility complex class I and II (MHC-I and -II), and in immunoprotection, suggesting alternative functions of these cells in a disease context. Importantly, we found that disease-specific oligodendroglia are also present in human MS brains and that a substantial number of genes known to be susceptibility genes for MS, so far mainly associated with immune cells, are expressed in the OL lineage cells. Finally, we demonstrate that OPCs can phagocytose and that MHC-II expressing OPCs can activate memory and effector CD4+ T cells. Our results suggest that OLs and OPCs are not passive targets but instead active immunomodulators in MS. The disease-specific OL lineage cells, for which we identify several biomarkers, may represent novel direct targets for immunomodulatory therapeutic approaches in MS.
登录
查看更多内容
影响因子：
64.8
作者：
Gregory, Adam P.;Dendrou, Calliope A.;Attfield, Kathrine E.;Haghikia, Aiden;Xifara, Dionysia K.;Butter, Falk;Poschmann, Gereon;Kaur, Gurman;Lambert, Lydia;Leach, Oliver A.;Proemel, Simone;Punwani, Divya;Felce, James H.;Davis, Simon J.;Gold, Ralf;Nielsen, Finn C.;Siegel, Richard M.;Mann, Matthias;Bell, John I.;McVean, Gil;Fugger, Lars
通讯作者：
Fugger, Lars
影响因子：
16.2
作者：
Kang, Shin H.;Fukaya, Masahiro;Yang, Jason K.;Rothstein, Jeffrey D.;Bergles, Dwight E.
通讯作者：
Bergles, Dwight E.
影响因子：
11.8
作者：
Marques S;van Bruggen D;Vanichkina DP;Floriddia EM;Munguba H;Väremo L;Giacomello S;Falcão AM;Meijer M;Björklund ÅK;Hjerling-Leffler J;Taft RJ;Castelo-Branco G
通讯作者：
Castelo-Branco G
DOI：
10.1093/bioinformatics/btp101
发表时间：
2009-04-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Bindea G;Mlecnik B;Hackl H;Charoentong P;Tosolini M;Kirilovsky A;Fridman WH;Pagès F;Trajanoski Z;Galon J
通讯作者：
Galon J
影响因子：
5.8
作者：
Angerer, Philipp;Haghverdi, Laleh;Buettner, Florian
通讯作者：
Buettner, Florian