实验性自身免疫性脑脊髓炎
神经保护
神经炎症
神经退行性变
神经科学
生物
多发性硬化
免疫系统
炎症
小胶质细胞
免疫学
中枢神经系统
医学
病理
疾病
作者
Myrto Andreadou,Florian Ingelfinger,Donatella De Feo,Teresa Cramer,Selma Tuzlak,Ekaterina Friebel,Bettina Schreiner,Pascale Eede,Shirin Schneeberger,Maria Geesdorf,Frederike Ridder,Christina A. Welsh,Laura Power,Daniel S. Kirschenbaum,Shiva K. Tyagarajan,Melanie Greter,Frank L. Heppner,Sarah Mundt,Burkhard Becher
标识
DOI:10.1038/s41593-023-01435-z
摘要
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.
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