title: Increased IL-23p19 expression in multiple sclerosis lesions and its induction in microglia.
abstract: 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.
authors.affiliation: Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Yonghai
authors.initials: Y
authors.lastname: Li
authors.forename: Niansheng
authors.initials: N
authors.lastname: Chu
authors.forename: Aihua
authors.initials: A
authors.lastname: Hu
authors.forename: Bruno
authors.initials: B
authors.lastname: Gran
authors.forename: Abdolmohamad
authors.initials: A
authors.lastname: Rostami
authors.forename: Guang-Xian
authors.initials: GX
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D017403:In Situ Hybridization; D053711:Interleukin-12 Receptor beta 1 Subunit / Q000378:metabolism; D053760:Interleukin-23 Subunit p19 / Q000096:biosynthesis* / Q000235:genetics; D008262:Macrophage Activation; D008264:Macrophages / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000378:metabolism*; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D053711:Interleukin-12 Receptor beta 1 Subunit; D053760:Interleukin-23 Subunit p19; D012333:RNA, Messenger