小柯机器人

美国加州大学圣迭戈分校Richard Daneman、旧金山分校Thomas D. Arnold等研究人员合作发现，中枢神经系统（CNS）的成纤维细胞在免疫细胞浸润时形成纤维化疤痕。相关论文于2021年2月1日发表在《自然—神经科学》杂志上。

在多发性硬化症的实验性自身免疫性脑脊髓炎（EAE）小鼠模型中，研究人员发现免疫细胞浸润后，中枢神经系统存在持续的纤维化瘢痕形成。通过在EAE中使用谱系追踪和单细胞测序，研究人员确定了大部分纤维化瘢痕均来自增殖性CNS成纤维细胞，而不是周细胞或浸润性骨髓衍生细胞。使用疱疹胸苷激酶的细胞特异性表达来去除增殖的纤维化细胞，可导致炎性病变内少突胶质细胞谱系细胞的增加和运动障碍的减少。

研究人员进一步发现，干扰素-γ途径基因在CNS纤维化细胞中富集，而Ifngr1的纤维化细胞特异性缺失导致EAE中纤维化瘢痕的减少。这些数据揭示了理解CNS纤维化反应的框架。 

据悉，纤维化是许多周围组织对炎症的常见病理反应，可以阻止组织再生和修复。

附：英文原文

Title: CNS fibroblasts form a fibrotic scar in response to immune cell infiltration

Author: Cayce E. Dorrier, Dvir Aran, Ezekiel A. Haenelt, Ryan N. Sheehy, Kimberly K. Hoi, Lucija Pintari, Yanan Chen, Carlos O. Lizama, Kelly M. Cautivo, Geoffrey A. Weiner, Brian Popko, Stephen P. J. Fancy, Thomas D. Arnold, Richard Daneman

Issue&Volume: 2021-02-01

Abstract: Fibrosis is a common pathological response to inflammation in many peripheral tissues and can prevent tissue regeneration and repair. Here, we identified persistent fibrotic scarring in the CNS following immune cell infiltration in the experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis. Using lineage tracing and single-cell sequencing in EAE, we determined that the majority of the fibrotic scar is derived from proliferative CNS fibroblasts, not pericytes or infiltrating bone marrow-derived cells. Ablating proliferating fibrotic cells using cell-specific expression of herpes thymidine kinase led to an increase in oligodendrocyte lineage cells within the inflammatory lesions and a reduction in motor disability. We further identified that interferon-gamma pathway genes are enriched in CNS fibrotic cells, and the fibrotic cell-specific deletion of Ifngr1 resulted in reduced fibrotic scarring in EAE. These data delineate a framework for understanding the CNS fibrotic response. Dorrier et al. identified fibrotic scarring in a mouse model of multiple sclerosis that arises from the proliferation of fibroblasts in the meninges and surrounding blood vessels, and determine that reducing scarring decreases motor symptom severity.

DOI: 10.1038/s41593-020-00770-9

Source: https://www.nature.com/articles/s41593-020-00770-9

Nature Neuroscience：《自然—神经科学》，创刊于1998年。隶属于施普林格·自然出版集团，最新IF：28.771
官方网址：https://www.nature.com/neuro/
投稿链接：https://mts-nn.nature.com/cgi-bin/main.plex