Brain Advance Access originally published online on September 26, 2006
Brain 2007 130(2):490-501; doi:10.1093/brain/awl273
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Increased IL-23p19 expression in multiple sclerosis lesions and its induction in microglia
1 Department of Neurology Philadelphia, PA, USA 2 Department of Anesthesiology, Thomas Jefferson University Philadelphia, PA, USA
Correspondence to: Guang-Xian Zhang, Department of Neurology, Thomas Jefferson University, 300 JHN Building, 900 Walnut Street, Philadelphia, PA, USA E-mail: guang-xian.zhang{at}jefferson.edu
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.
Key Words: multiple sclerosis; CNS; microglia; IL-23
Abbreviations:
APC, antigen presenting cell; DCs, dendritic cells; EAE, experimental autoimmune encephalomyelitis; ISH, in situ hybridization; LC, lesion centre; LE, lesion edge; LPS, lipopolysaccharide; NAWM, normal-appearing white matter; TNF-
, tumour necrosis factor-
Received March 31, 2006. Revised August 15, 2006. Accepted August 31, 2006.
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