2006 Fiscal Year Final Research Report Summary
A unique CD204^+ subpopulation of dendritic cells in NOD mice
| Project/Area Number |
17590911
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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 |
Metabolomics
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| Research Institution | Tohoku University |
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Principal Investigator |
TAKAHASHI Kazuma Tohoku University, Tohoku University, Hospital, Research Associate (60292215)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHINORI Hinokio Tohoku University, Hospital, Lecturer (10282071)
ISHI Naoto Tohoku University, Graduate School of Medicine, Assistant Professor (60291267)
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| Project Period (FY) |
2005 – 2006
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| Keywords | type 1 diabetes mellitus / dendritic cells / CD204 / Macrophage scavenger receptor |
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| Research Abstract |
Dendritic cells (DC) display defective function and phenotype in human type 1 diabetes, as well as in NOD mice and BB rats, and play crucial roles in the pathogenesis of this disease. To characterise molecular changes in bone marrow (BM)-derived DC from NOD, we compared transcript profiles of these cells with those from NON mice, and then found that BMDC from NOD express significantly higher level of CD204 than NON. Interestingly, CD204 on DC reportedly mediates a capacity to capture antigens from live cells referred to as nibbling. Strong expression of CD204 on NOD DC possibly leads to active antigen uptake from autologous cells, and then to the predisposition to autoimmunity. Focusing on this point, we here investigated the phenotype and function of CD204^+BM and splenic DC from NOD.
BM cells from 6-week-old female mice were cultivated in the presence of GM-CSF and IL-4 over 6 days. CD11c^+DC were sorted by magnetic beads-conjugated anti-CD11c antibodies. DC were phenotyped by a flow cytometer. Nibbling by BMDC was evaluated by monitoring the trafficking of plasma membrane between DiO- and DiD-labeled and unlabeled cells.
BMDC from NOD displayed 7 times higher mean fluorescence intensity of CD204, than normal strains (NOD 65.7±3.4, NON 8.2±0.34, C3H/HeN 8.0±0.55, Balb/c 9.0±0.49 ; P<0.05, Mann-Whitney U test). Among splenocytes, the proportion of CD204^+CD11c^+ DC from NOD was significantly higher than normal strains (NOD 0.65±0.09%, NON 0.10±0.02%, C3H/HeN 0.10± 0.02%, Balb/c 0.04±0.03% ; p<0.05). The phenotypes of CD204^+CDllc^+ BM and splenic DC were CD4^<low>CD8^-CD11b^<low>CD16/32^+CD19^<low>CD80^<high>CD86^<high>MHCclassI^+classII^+F4/80^+Gr-1^<low>. Unlabeled BMDC from NOD acquired fluorescently dual labeled membrane from other cells more rapidly than those from NON.
We propose that CD204 highly expressed in a unique subpopulation of DC from NOD possibly leads to active uptake of self-antigens, and then to the predisposition to autoimmune diseases in NOD.
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[Journal Article] Lack of association between IBD5 and Crohn's disease in Japanese patients demonstrates population-specific differences in inflammatory bowel disease2006
Author(s)
Tosa M, Negoro K, Kinouchi Y, Abe H, Nomura E, Takagi S, Aihara H, Oomori S, Sugimura M, Takahashi K, et al.
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Journal Title
Scand J Gastroenterol. 41・1
Pages: 48-53
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Lack of association between IBD5 and Crohn's disease in Japanese patients demonstrates population-specific differences in inflammatory bowel disease2006
Author(s)
Tosa M, Negoro K, Kinouchi Y, Abe H, Nomura E, Takagi S, Aihara H, Oomori S, Sugimura M, Takahashi K, et al.
-
Journal Title
Scand J Gastroenterol. 41(1)
Pages: 48-53
Description
「研究成果報告書概要(欧文)」より
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