Myeloid cell plasticity in the evolution of central nervous system autoimmunity.
Myeloid cell plasticity in the evolution of central nervous system autoimmunity.
复制标题
DOI：
10.1002/ana.25128
复制
发表时间：
2018-01
影响因子：
11.2
通讯作者：
Segal BM
中科院分区：
文献类型：
--
作者：
Giles DA;Washnock-Schmid JM;Duncker PC;Dahlawi S;Ponath G;Pitt D;Segal BM
骨髓细胞，包括巨噬细胞和树突状细胞，是多发性硬化症（MS）和实验性自身免疫性脑脊髓炎（EAE）动物模型中中枢神经系统（CNS）浸润的重要组成部分。虽然骨髓细胞通常被认为是促炎性的，但交替极化的亚群可以起到非炎性和/或修复功能。在这里，我们调查的异质性和生物学特性的骨髓细胞在中枢神经系统自身免疫。通过免疫组化分析慢性活动性MS病变中的髓样细胞表型。此外，在EAE加重和缓解期间从CNS分离免疫细胞，并通过流式细胞术、遗传和功能测定进行表征。在慢性活动性MS病变的活跃脱髓鞘边缘检测到表达iNOS（指示促炎表型）的骨髓细胞，而表达甘露糖受体（CD 206）（交替极化人类骨髓细胞的标志物）的巨噬细胞在静止的病变核心中富集。在EAE期间，CNS浸润的髓样细胞以及小胶质细胞在临床缓解之前立即从促炎性标志物的表达转变为非炎性标志物的表达。表达替代谱系标志物精氨酸酶-1（Arg 1）的小鼠CNS髓样细胞部分来源于iNOS+前体，与Arg 1 −对应物相比，缺乏激活致脑炎性T细胞。这些观察结果表明CNS髓样细胞的异质性，自身免疫性脱髓鞘疾病过程中的演变，以及它们在单细胞水平上的可塑性。MS患者疾病改良的未来治疗策略可能集中在加速CNS髓样细胞从促炎性表型向非炎性表型的转变。
Myeloid cells, including macrophages and dendritic cells, are a prominent component of central nervous system (CNS) infiltrates during multiple sclerosis (MS) and the animal model experimental autoimmune encephalomyelitis (EAE). Although myeloid cells are generally thought to be pro-inflammatory, alternatively-polarized subsets can serve non-inflammatory and/or reparative functions. Here we investigate the heterogeneity and biological properties of myeloid cells during central nervous system autoimmunity. Myeloid cell phenotypes in chronic active MS lesions were analyzed by immunohistochemistry. In addition, immune cells were isolated from the CNS during exacerbations and remissions of EAE and characterized by flow cytometric, genetic and functional assays. Myeloid cells expressing iNOS, indicative of a pro-inflammatory phenotype, were detected in the actively demyelinating rim of chronic active MS lesions, whereas macrophages expressing mannose receptor (CD206), a marker of alternatively-polarized human myeloid cells, were enriched in the quiescent lesion core. During EAE, CNS-infiltrating myeloid cells, as well as microglia, shifted from expression of pro- to non-inflammatory markers immediately prior to clinical remissions. Murine CNS myeloid cells expressing the alternative lineage marker arginase-1 (Arg1) were partially derived from iNOS+ precursors and were deficient in activating encephalitogenic T cells compared with their Arg1− counterparts. These observations demonstrate the heterogeneity of CNS myeloid cells, their evolution during the course of autoimmune demyelinating disease, and their plasticity on the single cell level. Future therapeutic strategies for disease modification in individuals with MS may be focused on accelerating the transition of CNS myeloid cells from a pro- to a non-inflammatory phenotype.
登录
查看更多内容
影响因子：
20.3
作者：
King, Irah L.;Dickendesher, Travis L.;Segal, Benjamin M.
通讯作者：
Segal, Benjamin M.
影响因子：
3.3
作者：
BO, L;MORK, S;TRAPP, BD
通讯作者：
TRAPP, BD
影响因子：
82.9
作者：
Greter, M;Heppner, FL;Becher, B
通讯作者：
Becher, B
影响因子：
25
作者：
Ajami, Bahareh;Bennett, Jami L.;Rossi, Fabio M. V.
通讯作者：
Rossi, Fabio M. V.
影响因子：
3.3
作者：
Benedek G;Zhang J;Bodhankar S;Nguyen H;Kent G;Jordan K;Manning D;Vandenbark AA;Offner H
通讯作者：
Offner H