2020年4月20日，《自然—免疫学》杂志在线发表了德国马克斯·德尔布吕克分子医学中心Alexander Mildner、以色列魏兹曼研究所Ido Amit等研究人员的合作研究。他们的工作表明，Cxcl10⁺单核细胞在自身免疫性神经炎症过程中定义了中枢神经系统的致病亚群。

Title: Cxcl10 + monocytes define a pathogenic subset in the central nervous system during autoimmune neuroinflammation

Author: Amir Giladi, Lisa Katharina Wagner, Hanjie Li, Dorothea Drr, Chiara Medaglia, Franziska Paul, Anat Shemer, Steffen Jung, Simon Yona, Matthias Mack, Achim Leutz, Ido Amit, Alexander Mildner

Issue&Volume: 2020-04-20

Abstract: Multiple sclerosis (MS) is characterized by pathological inflammation that results from the recruitment of lymphoid and myeloid immune cells from the blood into the brain. Due to subset heterogeneity, defining the functional roles of the various cell subsets in acute and chronic stages of MS has been challenging. Here, we used index and transcriptional single-cell sorting to characterize the mononuclear phagocytes that infiltrate the central nervous system from the periphery in mice with experimentally induced autoimmune encephalomyelitis, a model of MS. We identified eight monocyte and three dendritic cell subsets at acute and chronic disease stages in which the defined transcriptional programs pointed toward distinct functions. Monocyte-specific cell ablation identified Cxcl10+ and Saa3+ monocytic subsets with a pathogenic potential. Transfer experiments with different monocyte and precursor subsets indicated that these Cxcl10+ and Saa3+ pathogenic cells were not derived from Ly6C+ monocytes but from early myeloid cell progenitors. These results suggest that blocking specific pathogenic monocytic subsets, including Cxcl10+ and Saa3+ monocytes, could be used for targeted therapeutic interventions.

DOI: 10.1038/s41590-020-0661-1

Source: https://www.nature.com/articles/s41590-020-0661-1