瑞士苏黎世大学Burkhard Becher等研究人员合作发现，神经元中的IL-12传感可诱导小鼠神经保护性中枢神经系统组织适应并减轻神经炎症。相关论文于2023年9月25日在线发表于国际学术期刊《自然—神经科学》。
研究人员绘制了NK和T细胞以及神经元和少突胶质细胞的白细胞介素-12受体（IL-12R）表达图谱。在成年小鼠体内有条件地消减这些细胞类型的IL-12R并评估它们对实验性自身免疫性脑脊髓炎的易感性后发现，IL-12的神经保护作用是由神经外胚层衍生细胞介导的，特别是神经元，而不是免疫细胞。在多发性硬化症供体的人类脑组织中，研究人员观察到IL-12R的分布与小鼠相当，这表明小鼠和人类的机制相似。
结合流式细胞术、体细胞和单核 RNA 测序，研究人员揭示了IL-12诱导的神经保护性组织适应性，可防止早期神经变性，并在神经炎症期间维持营养因子的释放，从而维持小鼠中枢神经系统的完整性。
据介绍，IL-12是1型免疫的强大驱动者。矛盾的是，在自身免疫性疾病（包括中枢神经系统疾病）中，IL-12会减轻炎症反应。这些相反特性背后的潜在机制以及参与其中的细胞角色仍然难以捉摸。
附：英文原文
Title: IL-12 sensing in neurons induces neuroprotective CNS tissue adaptation and attenuates neuroinflammation in mice
Author: Andreadou, Myrto, Ingelfinger, Florian, De Feo, Donatella, Cramer, Teresa L. M., Tuzlak, Selma, Friebel, Ekaterina, Schreiner, Bettina, Eede, Pascale, Schneeberger, Shirin, Geesdorf, Maria, Ridder, Frederike, Welsh, Christina A., Power, Laura, Kirschenbaum, Daniel, Tyagarajan, Shiva K., Greter, Melanie, Heppner, Frank L., Mundt, Sarah, Becher, Burkhard
Issue&Volume: 2023-09-25
Abstract: Interleukin-12 (IL-12) is a potent driver of type 1 immunity. Paradoxically, in autoimmune conditions, including of the CNS, IL-12 reduces inflammation. The underlying mechanism behind these opposing properties and the involved cellular players remain elusive. Here we map IL-12 receptor (IL-12R) expression to NK and T cells as well as neurons and oligodendrocytes. Conditionally ablating the IL-12R across these cell types in adult mice and assessing their susceptibility to experimental autoimmune encephalomyelitis revealed that the neuroprotective role of IL-12 is mediated by neuroectoderm-derived cells, specifically neurons, and not immune cells. In human brain tissue from donors with multiple sclerosis, we observe an IL-12R distribution comparable to mice, suggesting similar mechanisms in mice and humans. Combining flow cytometry, bulk and single-nucleus RNA sequencing, we reveal an IL-12-induced neuroprotective tissue adaption preventing early neurodegeneration and sustaining trophic factor release during neuroinflammation, thereby maintaining CNS integrity in mice.
DOI: 10.1038/s41593-023-01435-z
Source: https://www.nature.com/articles/s41593-023-01435-z
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
本期文章：《自然—神经科学》：Online/在线发表
