Suppression of ongoing experimental autoimmune encephalomyelitis by neutralizing the function of the p28 subunit of IL-27 |
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Authors: | Goldberg Ruth Zohar Yaniv Wildbaum Gizi Geron Yifat Maor Gila Karin Nathan |
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Institution: | Department of Immunology, Bruce Rappaport Faculty of Medicine, Technion, Haifa 31096, Israel. |
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Abstract: | IL-27 is a recently defined family member of the long-chain, four-helix bundle cytokines, which consist of EBI3, an IL-12p40-related protein, and p28, an IL-12p35-related polypeptide. The role of IL-27 in the regulation of experimental autoimmune encephalomyelitis has never been studied. We show in this study that neutralizing the in vivo function of IL-27 by Abs against IL-27 p28 rapidly suppressed an ongoing long-lasting disease in C57BL/6 mice. These Abs were then used to determine the mechanistic basis of disease suppression. We show in this study that IL-27 is involved not only in the polarization of naive T cells undergoing Ag-specific T cell activation, but also in promoting the proliferation and IFN-gamma production by polarized T cells, including the long term Th1 line that has been previously selected against the target encephalitogenic determinant. This may explain in part why neutralizing IL-27 suppresses an already established disease in a very rapid and significant manner. |
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