A unique CD204^+ subpopulation of dendritic cells in NOD mice

NOD 小鼠中独特的 CD204^ 树突状细胞亚群

• 批准号: 17590911
• 负责人: TAKAHASHI Kazuma
• 金额: $ 2.24万
• 依托单位: Tohoku 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-17590911/
• 关键词: type 1 diabetes mellitus; dendritic cells; CD204; Macrophage scavenger receptor; CD204; 抗原提示細胞

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.

树突状细胞 (DC) 在人类 1 型糖尿病以及 NOD 小鼠和 BB 大鼠中表现出功能缺陷和表型缺陷，并在该疾病的发病机制中发挥着至关重要的作用。为了表征来自 NOD 的骨髓 (BM) 来源的 DC 的分子变化，我们将这些细胞的转录谱与来自 NON 小鼠的转录谱进行比较，然后发现来自 NOD 的 BMDC 表达的 CD204 水平显着高于 NON。有趣的是，据报道 DC 上的 CD204 介导从活细胞捕获抗原的能力，称为“蚕食”。 NOD DC 上 CD204 的强表达可能导致自体细胞主动摄取抗原，进而导致自身免疫的倾向。针对这一点，我们在此研究了来自 NOD 的 CD204^+BM 和脾 DC 的表型和功能。来自 6 周龄雌性小鼠的 BM 细胞在 GM-CSF 和 IL-4 存在下培养 6 天。 CD11c^+DC 通过磁珠缀合的抗 CD11c 抗体进行分选。通过流式细胞仪对DC进行表型分析。通过监测 DiO 和 DiD 标记细胞与未标记细胞之间质膜的运输来评估 BMDC 的蚕食。来自 NOD 的 BMDC 显示的 CD204 平均荧光强度比正常菌株高 7 倍（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，曼-惠特尼 U 检验）。脾细胞中，来自NOD的CD204^+CD11c^+ DC的比例显着高于正常菌株（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）。 CD204^+CDllc^+ BM和脾DC的表型为CD4^<low>CD8^-CD11b^<low>CD16/32^+CD19^<low>CD80^<high>CD86^<high>MHCclassI^+classII^+F4/80^+Gr-1^<low>。来自NOD的未标记BMDC比来自NON的细胞更快地从其他细胞获得荧光双标记膜。我们提出，在来自NOD的独特DC亚群中高表达的CD204可能导致自身抗原的主动摄取，然后导致NOD易患自身免疫性疾病。

项目成果

Lack of association between IBD5 and Crohn's disease in Japanese patients demonstrates population-specific differences in inflammatory bowel disease

日本患者中 IBD5 与克罗恩病之间缺乏关联，表明炎症性肠病存在人群特异性差异

• 发表时间: 2006
• 期刊: Scand J Gastroenterol. 41・1
• 作者: Tosa M;Negoro K;Kinouchi Y;Abe H;Nomura E;Takagi S;Aihara H;Oomori S;Sugimura M;Takahashi K;et al.
• 通讯作者: et al.

Secondary sulfonylurea failure: Comparison of period until insulin treatment between diabetic patients treated with gliclazide and glibenclamide

• DOI: 10.1016/j.diabres.2005.04.002
• 发表时间: 2005-12-01
• 期刊: DIABETES RESEARCH AND CLINICAL PRACTICE
• 影响因子: 5.1
• 作者: Satoh, J;Takahashi, K;Oka, Y
• 通讯作者: Oka, Y

Hypoglycemic effects of turmeric (Curcuma longa L. rhizomes) on genetically diabetic KK-Ay mice

• DOI: 10.1248/bpb.28.937
• 发表时间: 2005-05-01
• 期刊: BIOLOGICAL & PHARMACEUTICAL BULLETIN
• 影响因子: 2
• 作者: Kuroda, M;Mimaki, Y;Kitahara, M
• 通讯作者: Kitahara, M

Curcuminoids and sesquiterpenoids in turmeric (Curcuma longa L.) suppress an increase in blood glucose level in type 2 diabetic KK-Ay mice

• DOI: 10.1021/jf0483873
• 发表时间: 2005-02-23
• 期刊: JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
• 影响因子: 6.1
• 作者: Nishiyama, T;Mae, T;Kitahara, M
• 通讯作者: Kitahara, M

【対論糖尿病診療】 インスリンアナログの有用性Consアナログ製剤の特性を熟知して患者さんに最適な製剤を選択する.

【对话糖尿病治疗】胰岛素类似物的用处，熟悉类似物制剂的特点，选择最适合患者的制剂。

• 发表时间: 2006
• 期刊: 糖尿病診療マスター 4
• 作者: 高橋和眞;種田嘉信;小野利夫
• 通讯作者: 小野利夫