Molecular basis of lymphocyte migration to the skin and mechanisms of acquisition of skin-migrating activity

淋巴细胞迁移到皮肤的分子基础和获得皮肤迁移活性的机制

• 批准号: 17590433
• 负责人: HIRATA Takako
• 金额: $ 2.24万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590433/
• 关键词: T cells; Adhesion molecules; Selectins; Sialomucins; CD43; PSGL-1; Skin; Leukocyte rolling

The skin is the principal physical barrier against pathogens and foreign antigens. Under steady-state conditions, some memory T cells reside in the skin, but upon infection, effector T cells are promptly recruited to the skin, and play a central role in the host defense against pathogens. T cell localization to the skin also plays a key role in the pathogenesis of many inflammatory skin diseases, such as contact dermatitis, atopic dermatitis and psoriasis. The recruitment of effector/memory T cells to the skin is mediated by P-and E-selectin expressed on dermal vascular endothelium. Although we showed previously that P-selectin glycoprotein ligand-1 (PSGL-1) on T cells functions as the major P-selectin ligand and also as an E-selectin ligand, the molecular nature of E-selectin ligands other than PSGL-1 remains unknown. In this research project, we showed that a 130-kDa glycoprotein was precipitated by an E-selectin-IgG chimera from mouse Th1 cells. The mAb 1B11, which recognizes the 13 … More 0-kDa glycoform of CD43, recognized and depleted the 130-kDa band in the E-selectin-IgG precipitate, confirming its identity as CD43. E-selectin-dependent cell rolling on CD43 was observed under flow conditions using a CD43-IgG chimera. To clarify the function of CD43 as an E-selectin ligand in vivo, we generated mice deficient in both PSGL-1 and CD43. In migration assays in which adoptively transferred cells migrate to inflamed skin P-and E-selectin-dependently, CD43 contributed significantly to PSGL-1-independent Th1 cell migration. In addition, in vivo-activated T cells from the draining lymph nodes of sensitized mice deficient in PSGL-1 and/or CD43 showed significantly decreased E-selectin-binding activity and migration efficiency, with T cells from double-deficient mice showing the most profound decrease. Collectively, these results demonstrate that the CD43 expressed on activated T cells functions as an E-selectin ligand and thereby mediates T cell migration to inflamed sites, in collaboration with PSGL-1. Less

皮肤是抵抗病原体和外来抗原的主要物理屏障。在稳态条件下，一些记忆T细胞驻留在皮肤中，但在感染后，效应T细胞迅速被招募到皮肤，并在宿主防御病原体中发挥核心作用。T细胞定位于皮肤也在许多炎性皮肤病如接触性皮炎、特应性皮炎和银屑病的发病机制中起关键作用。效应/记忆T细胞向皮肤的募集由真皮血管内皮上表达的P-和E-选择素介导。虽然我们先前表明T细胞上的P-选择素糖蛋白配体-1（PSGL-1）作为主要的P-选择素配体并且也作为E-选择素配体起作用，但除PSGL-1之外的E-选择素配体的分子性质仍然未知。在本研究项目中，我们发现，130 kDa的糖蛋白沉淀的E-选择素-IgG嵌合体从小鼠Th 1细胞。mAb 1B 11识别13个 ...更多信息 0-CD 43的130-kDa糖型，识别并耗尽E-选择素-IgG沉淀物中的130-kDa条带，确认其为CD 43。使用CD 43-IgG嵌合体在流动条件下观察到E-选择素依赖性细胞在CD 43上滚动。为了阐明CD 43作为E-选择素配体在体内的功能，我们产生了PSGL-1和CD 43缺陷的小鼠。在迁移试验中，过继转移的细胞迁移到发炎的皮肤P-和E-选择素依赖性，CD 43显着PSGL-1-独立的Th 1细胞迁移。此外，来自PSGL-1和/或CD 43缺陷致敏小鼠引流淋巴结的体内活化T细胞显示出显著降低的E-选择素结合活性和迁移效率，其中来自双缺陷小鼠的T细胞显示出最显著的降低。总的来说，这些结果表明，在活化的T细胞上表达的CD 43作为E-选择素配体发挥作用，从而与PSGL-1合作介导T细胞迁移到发炎部位。少

项目成果

CCR7 is critically important for migration of dendritic cells in intestinal lamina propria to mesenteric lymph nodes

• 发表时间: 2006
• 作者: 寒川 延子

Hyaluronan oligosaccharides induce CD44 cleavage and promote cell migration in CD44-expressing tumor cells. In Hyaluronan - Its structure, metabolism, biological activities and therapeutic applications

透明质酸寡糖诱导 CD44 裂解并促进表达 CD44 的肿瘤细胞的细胞迁移。

• 发表时间: 2005
• 作者: Sugahara;KN;Murai T;Hirata T;Miyasaka M.
• 通讯作者: Miyasaka M.

CD43 collaborates with P-selectin glycoprotein ligand-1 to mediate E-selectin-dependent T cell migration to inflamed skin.

CD43 与 P-选择素糖蛋白配体-1 协同作用，介导 E-选择素依赖性 T 细胞迁移至发炎皮肤。

• 发表时间: 2007
• 期刊: J.Immunol. 178
• 作者: Matsumoto M;Shigeta A;Furukawa Y;Tanaka T;Miyasaka M;Hirata T.
• 通讯作者: Hirata T.

Hyaluronan oligosaccharides induce CD44 cleavage and promote cell migration in CD44-expressing tumor cells. In Hyaluronan-Its structure, metabolism, biological activities and therapeutic applications

透明质酸寡糖诱导 CD44 裂解并促进表达 CD44 的肿瘤细胞的细胞迁移。

• 发表时间: 2005
• 作者: Sugahara;KN;Murai T;Hirata T;Miyasaka M.
• 通讯作者: Miyasaka M.

P-selectin glycoprotein ligand-1 mediates L-selectin-dependent leukocyte rolling in high endothelial venules of peripheral lymph nodes

P-选择素糖蛋白配体-1介导L-选择素依赖性白细胞在周围淋巴结高内皮微静脉中滚动

• 发表时间: 2007
• 期刊: International Immunology 19
• 作者: Harakawa N;Shigeta A;Wato M;Merrill-Skoloff G;Furie BC;Furie B;Okazaki T;Domae N;Miyasaka M;Hirata T.
• 通讯作者: Hirata T.