Journal Article

Increased IL-23p19 expression in multiple sclerosis lesions and its induction in microglia

Yonghai Li, Niansheng Chu, Aihua Hu, Bruno Gran, Abdolmohamad Rostami and Guang-Xian Zhang

in Brain

Published on behalf of The Guarantors of Brain

Volume 130, issue 2, pages 490-501
Published in print February 2007 | ISSN: 0006-8950
Published online September 2006 | e-ISSN: 1460-2156 | DOI: http://dx.doi.org/10.1093/brain/awl273
Increased IL-23p19 expression in multiple sclerosis lesions and its induction in microglia

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IL-12 has long been considered important in the pathogenesis of multiple sclerosis. However, evidence from recent studies strongly supports the critical role of IL-12-related proinflammatory cytokine IL-23, but not IL-12, in the development of experimental autoimmune encephalomyelitis (EAE), an animal model of this disease. The role of IL-23 in the CNS immunity of multiple sclerosis patients has not been elucidated; nor is it known whether human microglia produce this cytokine. In this study we investigated the expression of IL-23p19 and p40, with its key subunit p19 as the focus, in histologically characterized CNS specimens from multiple sclerosis and control cases using in situ hybridization and immunohistochemistry. A significant increase in mRNA expression and protein production of both subunits of IL-23 was found in lesion tissues compared with non-lesion tissues. Double staining showed that activated macrophages/microglia were an important source of IL-23p19 in active and chronic active multiple sclerosis lesions. We also detected IL-23p19 expression in mature dendritic cells which were preferentially located in the perivascular cuff of active lesions. The finding that human microglia produce IL-23 was further confirmed by the inducible production of IL-23p19 and p40 in cultured human microglia in vitro upon different Toll-like receptor stimulations. Taken together, these findings on the expression of IL-23p19 in multiple sclerosis lesions may lead to a better understanding of the events culminating in human multiple sclerosis.

Keywords: multiple sclerosis; CNS; microglia; IL-23

Journal Article.  6661 words.  Illustrated.

Subjects: Neurology ; Neuroscience

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