Differential expression and regulation of IL-23 and IL-12 subunits and receptors in adult mouse microglia.

Publication/Presentation Date

11-15-2003

Abstract

IL-23 and IL-12 are functionally related heterodimeric cytokines that share the IL-12p40 subunit. IL-23 and IL-12 function through heterodimeric receptors, which share the IL-12Rbeta1 subunit. Production of IL-23, a heterodimer of IL-12p40 and IL-23p19, by CNS antigen-presenting cells (APC) is critical for susceptibility to experimental autoimmune encephalomyelitis (EAE), the animal model for multiple sclerosis (MS). We report that the expression of IL-23p19 mRNA is highly induced by stimulation with IFN-gamma and LPS in adult mouse microglia and a microglia cell line, EOC13. Expression of the IL-12R subunits, IL-12Rbeta1 and IL-12Rbeta2, is upregulated in both microglia and splenic macrophages upon stimulation with LPS or IFN-gamma and LPS, whereas the IL-23R subunit is upregulated only in macrophages. In EAE, an early peak of IL-23p19 mRNA expression is found in CD11b(+) CNS APC, compared with peripheral macrophages. In contrast, IL-12p40 and IL-12p35 mRNA maximum levels in the CNS are detected at peak of disease. The expression of IL-12p35 mRNA is more sustained than that of IL-12p40 and IL-23p19. Thus, IL-23 produced by CNS microglia/macrophages may contribute to the early induction of EAE. In the CNS, IL-23 may preferentially target infiltrating mononuclear cells, which upregulate IL-23R, rather than parenchymal microglia.

Volume

215

Issue

1-2

First Page

95

Last Page

103

ISSN

0022-510X

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

14568135

Department(s)

Administration and Leadership

Document Type

Article

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