| Project/Area Number |
15590336
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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 |
Experimental pathology
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
TAKAHARA Kazuhiko KYOTO UNIVERSITY, Lab.of Immunobiol., Dep.of Animal Development and Physiology, Division of Systemic Life Science, Graduate School of Biostudies, Lecturer, 生命科学研究科, 講師 (90301233)
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| Co-Investigator(Kenkyū-buntansha) |
INABA Kayo KYOTO UNIVERSITY, Lab.of Immunobiol., Dep.of Animal Development and Physiology, Division of Systemic Life Science, Graduate School of Biostudies, Professor, 生命科学研究科, 教授 (00115792)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2004: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2003: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | Dendritic cells / Langerhans cells / Langerin / C-type lectin / Microbe recognition / C.albicans / zymosan / Phagocytosis |
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| Research Abstract |
Langerin (CD207) is a type II C-type lectin that is expressed in epidermal dendritic cells (Langerhans cells ; LC). In this project, we performed functional analyses as an antigen and microbe uptake receptor of CD207 in comparison with other type II C-type lectins in mouse DC-SIGN family, such as SIGNR1, SIGNR3 and mDC-SIGN.
1)Internalization of tagged-CD207 molecule by cross-linking with anti-tag antibody was observed by cytofluorometer and fluorescent microscope. In comparison with the lectins in DC-SIGN family, CD207 showed the strongest internalizing activity comparable with SIGNR3. Internalized antibody via CD207 was sorted into intracellular vesicle distinct from CD71^+ early endosome and CD107^+ late endosome, suggesting that antigens captured by CD207 are processed differently from those via MMR and CD205.
2)CD207-transfectants captured dextran and OVA. These activities were inhibited by GlcNAc and Fucose as well as mannan. So CD207 is a typical mannose/mannan type lectin.
3)The transfectants recognized zymosan and heat-killed C.albicans, in a mannan-dependent manner. Unlike SIGNR1, CD207 was incapable of recognizing Gram-negative bacteria, such as E.coli and S.typhimurium.
4)Internalization of the yeast particles via CD207 was confirmed by a quenching method of extracellular particles using acidic trypan blue.
5)CD207 was shown to physically associate with TLR2, which formed heterodimer with TLR1 or TLR6 to mediate activation signal by various substances from microbes.
Collectively, our results indicate that CD207 possibly play a role as an antigen receptor to capture and process polysaccha-rides, glycoproteins and microbes. In addition, CD207 might be involved in TLR2-dependent cellular responses against pathogen.
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