IL-27 subunits and its receptor (WSX-1) mRNAs are markedly up-regulated in inflammatory cells in the CNS during experimental autoimmune encephalomyelitis

IL-27 (EBI3p28) is a recently discovered heterodimeric cytokine, which is functionally related to IL-23p40p19 and IL-12p40p35. IL-27 acts in synergy with IL-12 early during Th1 development from naïve T cells. IL-27 functions through the WSX-1 and the gpl30 receptor subunits, which shares homology with the IL-12Rβ2 subunit. We have previously reported that IL-23 is up-regulated in CD11b+ microglia/macrophages in the CNS during the early phase of experimental autoimmune encephalomyelitis (EAE), and thus may contribute to the early induction of EAE. In the present study, we examined the expression of IL-27 and its receptor in the CNS, spleen, and lymph nodes at different stages of EAE actively induced with myelin oligodendrocyte glycoprotein peptide35-55. Our findings show that IL-27 EBI3 and p28 mRNA were up-regulated to a maximum level at the peak of disease in APC from the CNS and lymph nodes, but not in the spleen. Moreover, IL-27 receptor (WSX-1) expression was greatly up-regulated during the early stage of EAE in both the CNS and lymph nodes. Taken together, our data show that subunits of IL-27 and its receptor (WSX-1) mRNAs are markedly up-regulated in inflammatory cells in the CNS at the peak of disease. Thus, IL-27 produced by infiltrating cells in the CNS may regulate in a paracrine manner the Th1 response in EAE.