| Project/Area Number |
26460493
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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 |
Experimental pathology
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| Research Institution | Toin University of Yokohama (2016)
Juntendo University (2014-2015) |
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Principal Investigator |
LIN QINGSHUN 桐蔭横浜大学, 医用工学部, 客員研究員 (00468589)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | ループス腎炎 / 自己免疫寛容破綻 / 細胞特異的FcγRIIB欠損 / B細胞 / 単球/マクロファージ / 樹状細胞 / B細胞活性化因子 / IL-1b,IL-10,CLcf1 / FcgRIIB発現欠損 / 単球 / RNA-seq / IL-1β,IL-10,CLcf1 / FcγRIIB / 細胞特異的FcγRIIB欠損マウス / Monocyte/マクロファージ / B細胞の自己免疫寛容破綻 / サイトカイン / monocyte/マクロファージ |
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| Outline of Final Research Achievements |
C57BL/6 mice carrying the Yaa autoimmune susceptibility locus spontaneously develop lethal lupus nephritis when the FcγRIIb gene is deleted (B6.FcγRIIb-/-.Yaa). To define the cell type specific role of FcγRIIb in the disease, we established B cell (CD19Cre.Yaa), myeloid cell (C/EBPαCre.Yaa), and dendritic cells (DC) (CD11cCre.Yaa) specific FcγRIIb-deficient B6.Yaa mouse strains. CD19Cre.Yaa mice developed milder lupus nephritis compared to B6.FcγRIIb-/-.Yaa mice, indicating that FcγRIIb deficiency on only B cells is not sufficient for the development of severe disease. Surprisingly, C/EBPαCre.Yaa mice developed similar mild disease as CD19Cre.Yaa mice whereas CD11cCre.Yaa stayed disease free. These observations indicate that, in B6. FcγRIIb-/-.Yaa mice, FcγRIIb deficiency on both B cells and myeloid cells, but not on DCs, contribute to the development of severe lupus with high autoantibody titers.
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