2017 Fiscal Year Final Research Report
Novel therapeutic target molecules in Sjogren's syndrome: NR4A2 and DPP4
| Project/Area Number |
16K20934
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Collagenous pathology/Allergology
Pathobiological dentistry/Dental radiology
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| Research Institution | University of Tsukuba |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Keywords | シェーグレン症候群 / Th17細胞 |
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| Outline of Final Research Achievements |
To clarify a role of NR4A2 and DPP4 in the pathogenesis of Sjogren’s syndrome (SS), 1) I examined mRNA expression of NR4A2 and DPP4 in labial salivary glands (LSGs) of SS, IgG4-related disease (IgG4-RD) and healthy controls (HC) by qPCR and the protein expression in the LSGs by immunofluorescence staining (IF), and 2) performed functional analysis of the gene using peripheral CD4+ T cells of SS patients. 1) NR4A2 was significantly higher in LSGs of SS than controls, while DPP4 was not. IF revealed higher NR4A2 in CD4+ T cells and IL-17-producing cells in LSGs of SS compared with IgG4-RD. 2) Peripheral CD4+ T cells showed significantly increased NR4A2 mRNA and Th17 polarization in SS compared with HC. Nuclear NR4A2 in Th17-polarized CD4+ T cells was significantly higher in SS than in HC. Importazole, inhibiting nuclear NR4A2, suppressed Th17 polarization and IL-21 mRNA in CD4+ T cells under Th17-polarizing conditions. Thus, NR4A2 could contribute to enhanced Th17 polarization in SS.
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| Free Research Field |
膠原病学
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