2007 Fiscal Year Final Research Report Summary
Analysis of the CD47-SHPS-1 signaling system in autoimmune disease
| Project/Area Number |
18591098
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
膠原病・アレルギー・感染症内科学
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| Research Institution | Gunma University |
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Principal Investigator |
KANEKO Yoriaki Gunma University, Graduate School of Medicine, Assistant Professor (00334095)
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| Project Period (FY) |
2006 – 2007
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| Keywords | SHPS-1 / CD47 / ITIM / macrophage / dendritic cells / NKT / autoimmunity |
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| Research Abstract |
Src homology 2 domain-containing protein tyrosine phosphatase substrate-1 (SHPS-1), which is originally identified as a substrate for protein tyrosine phosphatases SHP-1 and SHP-2, is a member of immunoglobulin superfamily. SHPS-1 contains ITIM in its intracellular domain and its extra-cellular region interacts with CD47, which is widely expressed on immune cells. The interaction between CD47 and SHPS-1 constitutes a cell-cell communication system (the CD47-SHPS-1 signaling system) that may function in regulation of a variety of biological responses. SHPS-1 is predominantly exposed on macrophages and dendritic cells (DCs), and the CD47-SHPS-1 signaling system is considered to be a negative regulator of immune responses. We investigated the physiological roles of SHPS-1 by the use of SHPS-1 mutant mice, which lack most of the cytoplasmic region of its protein and we revealed some important functions. SHPS-1 negatively regulates the phagocytosis of RBCs by splenic macrophages and it determines both the lifespan of individual RBCs and the number of circulating erythrocytes. SHPS-1 on DCs is essential for both priming of naive T cells and the activation of NKT cells. SHPS-1 positively regulates the development of autoimmune disease and α-GalCer-induced anti-metastatic activities. These results indicate the CD47-SHPS-1 signaling system plays important roles in immune responses.
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