MOG-Specific T Cells Lead to Spontaneous EAE with Multilocular B Cell Infiltration in the GF-IL23 Model

• Published in: Neuromolecular medicine Vol. 24; no. 4; pp. 415 - 423
• Main Authors: Nitsch, Louisa, Petzinna, Simon, Zimmermann, Julian, Getts, Daniel R., Becker, Albert, Müller, Marcus
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.12.2022; Springer Nature B.V
• Subjects: Ataxia; Biomedical and Life Sciences; Biomedicine; Central nervous system; Cerebellum; Demyelination; Experimental allergic encephalomyelitis; Immunization; Inflammation; Interleukin 23; Internal Medicine; Lymphocytes B; Lymphocytes T; Multiple sclerosis; Myelin; Myelitis; Neurology; Neurosciences; Oligodendrocyte-myelin glycoprotein; Original Paper; Signal transduction; T cell receptors; Autoimmunity; Neuroinflammation; B cells; 2D2 mice; IL-23
• ISSN: 1535-1084; 1559-1174
• DOI: 10.1007/s12017-022-08705-2

Although IL-23 and downstream signal transduction play essential roles in neuroinflammation, the local impact of IL-23 in multiple sclerosis is still not fully understood. Our previous study revealed that the central nervous system (CNS)-restricted expression of IL-23 in a mouse model with astrocyte-specific expression of IL-23, called GF-IL23 mice, leads to spontaneous formation of infiltrates in the brain, especially in the cerebellum. To further investigate the impact of CNS-specific IL-23-expression on neuroinflammation, we studied the GF-IL23 model in mice expressing a myelin oligodendrocyte glycoprotein (MOG)-specific T cell receptor (GF23-2D2 mice). The GF23-2D2 mice developed a chronic progressive experimental autoimmune encephalomyelitis with myelitis and ataxia without requiring additional immunization. CNS-production of IL-23 alone induced pronounced neuroinflammation in the transgenic MOG-specific T cell receptor model. The GF23-2D2 mice spontaneously developed multilocular infiltrates with a high number of B cells, demyelination and a proinflammatory cytokine milieu indicating that the interaction of encephalitogenic T cells and B cells via co-stimulatory factors seemed to be crucial.