2017 Fiscal Year Final Research Report
A novel role for EBI3, a common subunit of IL-27 and IL-35, as a intracellular molecule in the augmentation of IL-23Ra protein expression
| Project/Area Number |
15K07947
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Tokyo Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
善本 隆之 東京医科大学, 医学部, 教授 (80202406)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | EBI3 / IL-23Ra / カルネキシン |
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| Outline of Final Research Achievements |
We explored an intracellular role of Epstein-Barr virus-induced gene 3 (EBI3) independent of function as cytokines. EBI3-deficient naive CD4+ T cells had reduced interferon (IFN)-γ production and failed to induce T cell-dependent colitis in mice. Similarly reduced IFN-γ production was observed in vitro in EBI3-deficient CD4+ T cells differentiated under pathogenic helper T 17 polarizing conditions with IL-23 because of decreased expression of IL-23 receptor α (IL-23Rα) at the protein level but not the mRNA level. EBI3 augmented IL-23Rα expression via binding to the chaperone molecule calnexin and to IL-23Rα. However, EBI3 poorly augmented the expression of G149R, an IL-23Rα variant that protects against the development of human colitis, because binding of EBI3 to the variant was significantly reduced. These results suggest that EBI3 plays a critical role in augmenting IL-23Rα protein expression via calnexin under inflammatory conditions.
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| Free Research Field |
Immunology
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