实验性自身免疫性脑脊髓炎
神经保护
神经炎症
免疫系统
多发性硬化
炎症
生物
神经科学
中枢神经系统
免疫学
神经外胚层
脑脊髓炎
小胶质细胞
胚胎干细胞
遗传学
基因
中胚层
作者
Myrto Andreadou,Florian Ingelfinger,Donatella De Feo,Ekaterina Friebel,Selma Tuzlak,Teresa Cramer,Bettina Schreiner,Pascale Eede,Shirin Schneeberger,Maria Geesdorf,Frederike Ridder,Christina A. Welsh,Daniel S. Kirschenbaum,Shiva K. Tyagarajan,Melanie Greter,Frank L. Heppner,Sarah Mundt,Burkhard Becher
标识
DOI:10.1101/2022.09.14.506749
摘要
Abstract IL-12 is a well-established driver of type 1 immune responses. Paradoxically, in several autoimmune conditions including neuroinflammation, IL-12 reduces pathology and exhibits regulatory properties. Yet, the mechanism and the involved cellular players behind this immune regulation remain elusive. To identify the IL-12-responsive elements which prevent immunopathology, we generated mouse models lacking a functional IL-12 receptor either in all cells or in specific populations within the immune or central nervous system (CNS) compartments, and induced experimental autoimmune encephalomyelitis (EAE), which models human Multiple Sclerosis (MS). This revealed that the CNS tissue-protective features of IL-12 are mediated by cells of the neuroectoderm, and not immune cells. Importantly, sections of brain from patients with MS show comparable patterns of expression, indicating parallel mechanisms in humans. By combining spectral flow cytometry, bulk and single-nucleus RNA sequencing, we uncovered an IL-12-induced neuroprotective adaption of the neuroectoderm critically involved in maintaining CNS tissue integrity during inflammation.
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