近期，国际著名学术期刊《自然医学》（Nature Medicine）最新一期发表了健康所钱友存研究员对于学术论文“Peli1 promotes microglia-mediated CNS inflammation by regulating Traf3 degradation”的题为“Peli1 sets the CNS on fire”的精彩点评。
多发性硬化（Multiple Sclerosis，MS）是一种中枢神经系统炎症损伤性自身免疫病，其发病机制尚不清楚。小神经胶质细胞（microglia）在MS炎症性病理中发挥着关键性作用。钱友存研究员综合分析了相关研究领域进展，强调了该研究成果的重要意义在于通过小鼠疾病模型研究发现调控小神经胶质细胞激活的关键调节因子Peli1，并阐明其在调控MS病理中的功能与作用机制，为MS及相关疾病的治疗提供了重要理论基础与潜在新靶点，并讨论了尚待进一步解决的关键科学问题及针对性研发治疗新策略的措施。(生物谷Bioon.com)
生物谷推荐英文摘要1：
Nature Medicine doi:10.1038/nm.3176
Peli1 sets the CNS on fire
It has long been unknown how activation of resident macrophages in the brain, or microglia, is regulated during the inflammatory pathogenesis of multiple sclerosis. Work in a mouse model of human multiple sclerosis identifies the E3 ubiquitin ligase Peli1 as a new crucial regulator of microglia activation
生物谷推荐英文摘要2：
Nature Medicine doi:10.1038/nm.3111
Peli1 promotes microglia-mediated CNS inflammation by regulating Traf3 degradation
Microglia are crucial for the pathogenesis of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). Here we show that the E3 ubiquitin ligase Peli1 is abundantly expressed in microglia and promotes microglial activation during the course of EAE induction. Peli1 mediates the induction of chemokines and proinflammatory cytokines in microglia and thereby promotes recruitment of T cells into the central nervous system. The severity of EAE is reduced in Peli1-deficient mice despite their competent induction of inflammatory T cells in the peripheral lymphoid organs. Notably, Peli1 regulates Toll-like receptor (TLR) pathway signaling by promoting degradation of TNF receptor–associated factor 3 (Traf3), a potent inhibitor of mitogen-activated protein kinase (MAPK) activation and gene induction. Ablation of Traf3 restores microglial activation and CNS inflammation after the induction of EAE in Peli1-deficient mice. These findings establish Peli1 as a microglia-specific mediator of autoimmune neuroinflammation and suggest a previously unknown signaling mechanism of Peli1 function.
