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More MS news articles for October 2003

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

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14568135&dopt=Abstract

J Neurol Sci. 2003 Nov 15;215(1-2):95-103
Li J, Gran B, Zhang GX, Ventura ES, Siglienti I, Rostami A, Kamoun M.
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 3400 Spruce Street, 19104, Philadelphia, PA, USA

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.