2006 Fiscal Year Final Research Report Summary
Molecular basis of lymphocyte migration to the skin and mechanisms of acquisition of skin-migrating activity
| Project/Area Number |
17590433
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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 |
Immunology
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| Research Institution | Osaka University |
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Principal Investigator |
HIRATA Takako Osaka University, Research Institute for Microbial Diseases, Specially appointed associate professor, 微生物病研究所, 特任助教授 (00346199)
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| Co-Investigator(Kenkyū-buntansha) |
MIYASAKA Masayuki Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (50064613)
SHIGETA Akiko Osaka University, Research Institute for Microbial Diseases, Specially appointed research associate, 微生物病研究所, 特任研究員 (50420435)
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| Project Period (FY) |
2005 – 2006
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| Keywords | T cells / Adhesion molecules / Selectins / Sialomucins / CD43 / PSGL-1 / Skin / Leukocyte rolling |
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| Research Abstract |
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
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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
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[Journal Article] Nepmucin, a novel HEV sialomucin, mediates L-selectin-dependent lymphocyte rolling and promotes lymphocyte adhesion under flow2006
Author(s)
Umemoto E, Tanaka T, Kanda H, Jin S, Tohya K, Otani K, Matsutani T, Matsumoto M, Ebisuno Y, Jang MH, Fukuda M, Hirata T, Miyasaka M.
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Journal Title
Journal of Experimental Medicine 203
Pages: 1603-1614
Description
「研究成果報告書概要(和文)」より
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[Journal Article] CCR7 is critically important for migration of dendritic cells in intestinal lamina propria to mesenteric lymph nodes2006
Author(s)
Jang MH, Sougawa N, Tanaka T, Hirata T, Hiroi T, Tohya K, Guo Z, Umemoto E, Ebisuno Y, Yang B, Seoh J, Lipp M, Kiyono H, Miyasaka M.
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Journal Title
Journal of Immunology 176
Pages: 803-810
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Nepmucin, a novel HEV sialomucin, mediates L-selectin-dependent lymphocyte rolling and promotes lymphocyte adhesion under flow.2006
Author(s)
Umemoto E, Tanaka T, Kanda H, Jin S, Tohya K, Otani K, Matsutani T, Matsumoto M, Ebisuno Y, Jang MH, Fukuda M, Hirata T, Miyasaka M.
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Journal Title
J.Exp.Med. 203
Pages: 1603-1614
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] CCR7 is critically important for migration of dendritic cells in intestinal lamina propria to mesenteric lymph nodes.2006
Author(s)
Jang MH, Sougawa N, Tanaka T, Hirata T, Hiroi T, Tohya K, Guo Z, Umemoto E, Ebisuno Y, Yang B, Seoh J, Lipp M, Kiyono H, Miyasaka M.
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Journal Title
J.Immunol. 176
Pages: 803-810
Description
「研究成果報告書概要(欧文)」より
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