Analysis of the CD47-SHPS-1 signaling system in autoimmune disease

自身免疫性疾病中CD47-SHPS-1信号系统的分析

• 批准号: 18591098
• 负责人: KANEKO Yoriaki
• 金额: $ 2.43万
• 依托单位: Gunma University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591098/
• 关键词: SHPS-1; CD47; ITIM; macrophage; dendritic cells; NKT; autoimmunity; 実験的自己免疫性脳脊髄炎; Th-17; NKT細胞; α-GalCer; 肺転移

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.

含有 Src 同源 2 结构域的蛋白酪氨酸磷酸酶底物-1 (SHPS-1) 最初被鉴定为蛋白酪氨酸磷酸酶 SHP-1 和 SHP-2 的底物，是免疫球蛋白超家族的成员。 SHPS-1的胞内区域含有ITIM，其胞外区域与广泛表达于免疫细胞上的CD47相互作用。 CD47 和 SHPS-1 之间的相互作用构成了细胞间通讯系统（CD47-SHPS-1 信号系统），可能在调节多种生物反应中发挥作用。 SHPS-1 主要暴露于巨噬细胞和树突状细胞 (DC)，CD47-SHPS-1 信号系统被认为是免疫反应的负调节因子。我们通过使用 SHPS-1 突变小鼠研究了 SHPS-1 的生理作用，该突变小鼠缺乏其蛋白质的大部分细胞质区域，并揭示了一些重要的功能。 SHPS-1 负向调节脾巨噬细胞对红细胞的吞噬作用，并决定单个红细胞的寿命和循环红细胞的数量。 DC 上的 SHPS-1 对于初始 T 细胞的启动和 NKT 细胞的激活至关重要。 SHPS-1 积极调节自身免疫性疾病的发展和 α-GalCer 诱导的抗转移活性。这些结果表明CD47-SHPS-1信号系统在免疫反应中发挥重要作用。

项目成果

Regulation by Src homology 2 domain-containing protein tyrosine phosphatase substrate-1 of α-galactosylceramide-induced antimetastatic activity and Th1 and Th2 responses of NKT cells

• DOI: 10.4049/jimmunol.178.10.6164
• 发表时间: 2007-05-15
• 期刊: JOURNAL OF IMMUNOLOGY
• 影响因子: 4.4
• 作者: Okajo, Jun;Kaneko, Yoriaki;Nojima, Yoshihisa
• 通讯作者: Nojima, Yoshihisa

Enhanced phagocytosis of CD47-deficient red blood cells by spienic macrophages requires SHPS-1

精神巨噬细胞增强 CD47 缺陷红细胞的吞噬作用需要 SHPS-1

• 发表时间: 2007
• 期刊: Biochem Biophys Res Commun 343(4)
• 作者: Ishikawa-Sekigami T;Kaneko Y;et. al.
• 通讯作者: et. al.

Regulation by SHPS-1 of α-GalCer-induced antimetastatic activity and Th1 and Th2 responses of natural killer T cells.

SHPS-1 对 α-GalCer 诱导的抗转移活性以及自然杀伤 T 细胞的 Th1 和 Th2 反应的调节。

• 发表时间: 2007
• 期刊: J. Immunol. 178
• 作者: Okajo;J.;et. al.
• 通讯作者: et. al.

Resistance to collagen-induced arthritis in SHPS-1 mutant mice

• DOI: 10.1016/j.bbrc.2008.04.124
• 发表时间: 2008-07-04
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Okuzawa, Chie;Kaneko, Yoriaki;Nojima, Yoshihisa
• 通讯作者: Nojima, Yoshihisa

Resistance to experimental autoimmune encephalomyelitis and impaired T cell priming by dendritic cells in SHPS-1 mutant mice.

SHPS-1 突变小鼠中树突状细胞对实验性自身免疫性脑脊髓炎的抵抗力和 T 细胞启动受损。

• 发表时间: 2007
• 期刊: J. Immunol. 179
• 作者: Tomizawa;T.;Kaneko;Y.;Kaneko;Y.;Saito;Y.;Ohnishi;H.;Okajo;J.;Okuzawa;C.;Ishikawa-Sekigami;T.;Murata;Y.;Okazawa;H.;Okamoto;K.;Nojima;Y. Matozaki;T.
• 通讯作者: T.