2006 Fiscal Year Final Research Report Summary
Adhesive interactions governing immune-cell trafficking across HEVs and its regulation by infectious stimulation
| Project/Area Number |
17590432
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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 |
TANAKA Toshiyuki Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (30217054)
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| Project Period (FY) |
2005 – 2006
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| Keywords | lymphocyte homing / lymph nodes / high endothelial venules / cell adhesion / chemokine / rolling / nepmucin / L-selectin |
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| Research Abstract |
Trafficking of lymphocytes and certain antigen presenting cells from the blood into lymph nodes (LN) is mediated by a cascade of adhesive interactions between circulating immune-cells and high endothelial venules (HEVs). The adhesive interactions include rolling, firm adhesion and transendothelial migration of immune-cells across the HEVs. Molecular mechanisms governing the adhesive interactions still remain to be fully elucidated. Here we addressed two following issues. (1)Functional significance of a novel sialomucin nepmucin in lymphocyte homing to LNs. We identified a novel HEV-associated sialomucin, nepmucin (mucin not expressed in Peyer's patches). Unlike conventional sialomucins, nepmucin contains a single V-type Ig domain and a mucin-like domain. In LN HEVs, nepmucin is decorated by L-selectin-reactive sugar chains. We found that nepmucin modified with L-selectin-reactive oligosaccharides in its mucin-like domain supported lymphocyte rolling under physiological flow conditions.
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Furthermore, nepmucin bound lymphocytes via its Ig domain, apparently independent of lymphocyte LFA-1 and VLA-4,and promoted shear-resistant lymphocyte binding in combination with ICAM-1. Taken together, these results suggest that nepmucin may serve as a dual-functioning adhesion molecule in LN HEVs, mediating both lymphocyte rolling and binding via different functional domains. (2)Adhesive interactions between plasmacytoid dendritic cells (pDCs) and HEVs. pDCs are natural type I interferon-producing cells, and are found in LNs, where they support both innate and adaptive immune responses. We found that LFA-1/VLA-4 on pDCs and their ligands on HEVs play critical roles in the adhesion and transmigration process of pDCs. We also found that signals through CCR7 play an important role in homeostatic trafficking of pDCs into LNs across HEV cells. These observations collectively suggest that certain cell adhesion molecules and chemokine signals cooperatively regulate trafficking of pDCs across HEVs. Less
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Research Products
(15 results)
