以色列魏茨曼科学研究所Steffen Jung取得最新进展。他们发现白细胞介素10（IL-10）可预防周围内毒素处理的病理小胶质细胞过度活化。2020年10月12日出版的国际知名学术期刊《免疫》发表了这一成果。

他们探讨了IL-10轴在外周内毒素处理后，恢复小鼠小胶质细胞稳态的作用。具体来说，他们表明脂多糖（LPS）处理的小鼠小胶质细胞表现出IL-10受体缺陷，这些小胶质细胞出现神经元损伤和易患致命疾病。小胶质细胞肿瘤坏死因子（TNF）缺陷后，反而拯救了这些动物，这表明基于小胶质细胞的回路驱动病理。单细胞转录组分析揭示了中枢神经系统（CNS）中产生IL-10的各种免疫细胞，包括最显著的Ly49D + NK细胞和中性粒细胞，但没有小胶质细胞。

他们共同定义了小胶质细胞应答周围内毒素的动力学，包括其激活和强大的沉默，并突出了非小胶质细胞IL-10在防止有害小胶质细胞过度活化中的关键作用。

研究人员表示，小胶质细胞是脑实质的常驻巨噬细胞，是CNS发育，体内稳态和疾病的关键因素。不同的脑部病理似乎与离散的小胶质细胞激活模块有关。处理后小胶质细胞如何恢复静止尚不清楚。

附：英文原文

Title: Interleukin-10 Prevents Pathological Microglia Hyperactivation following Peripheral Endotoxin Challenge

Author: Anat Shemer, Isabelle Scheyltjens, Gal Ronit Frumer, Jung-Seok Kim, Jonathan Grozovski, Serkalem Ayanaw, Bareket Dassa, Hannah Van Hove, Louise Chappell-Maor, Sigalit Boura-Halfon, Dena Leshkowitz, Werner Mueller, Nicola Maggio, Kiavash Movahedi, Steffen Jung

Issue&Volume: 2020-10-12

Abstract: Microglia, the resident macrophages of the brain parenchyma, are key players in centralnervous system (CNS) development, homeostasis, and disorders. Distinct brain pathologiesseem associated with discrete microglia activation modules. How microglia regain quiescencefollowing challenges remains less understood. Here, we explored the role of the interleukin-10(IL-10) axis in restoring murine microglia homeostasis following a peripheral endotoxinchallenge. Specifically, we show that lipopolysaccharide (LPS)-challenged mice harboringIL-10 receptor-deficient microglia displayed neuronal impairment and succumbed tofatal sickness. Addition of a microglial tumor necrosis factor (TNF) deficiency rescuedthese animals, suggesting a microglia-based circuit driving pathology. Single celltranscriptome analysis revealed various IL-10 producing immune cells in the CNS, includingmost prominently Ly49D+ NK cells and neutrophils, but not microglia. Collectively, we define kinetics ofthe microglia response to peripheral endotoxin challenge, including their activationand robust silencing, and highlight the critical role of non-microglial IL-10 in preventingdeleterious microglia hyperactivation.

DOI: 10.1016/j.immuni.2020.09.018

Source: https://www.cell.com/immunity/fulltext/S1074-7613(20)30412-X