The roles of PRR and cytokines in the development of intestinal microbiota-dependent inflammatory bowel diseases

PRR 和细胞因子在肠道菌群依赖性炎症性肠病发生中的作用

• 批准号: 23700508
• 负责人: TANG Ce
• 金额: $ 2.83万
• 依托单位: Tokyo University of Science (2012)The University of Tokyo (2011)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23700508/
• 关键词: C型レクチン; 腸内細菌叢; サイトカイン; 炎症性腸疾患; 遺伝子欠損マウス; Ｃ型レクチン

The intestinal immune system has to take dual tasks; the system should fight against invading pathogens and, at the same time, the system should be tolerant toward commensal microbiota or food components. Dectin-1 is the receptor for beta-glucans expressed in fungal cell walls and activates the immune system toprevent infection. Because beta-glucans are contained in wide variety of foods and commensal microbiota, we investigated the effects of Dectin-1 signaling on the intestinal immunity. We found that Dectin-1-deficient mice were refractory to dextran sodium sulfate-induced colitis, a model for inflammatory bowel diseases, due to expansion of one genus of Gram-positive commensal bacteria in the colon associated with remodification of T cell subpopulations. Furthermore, oral administration of a seaweed-derived Dectin-1 antagonist, inhibited the proinflammatory cytokine production in colonic lamina propria cells and suppressed the development of colitis. These observations suggest that inhibition of Dectin-1 signaling in the colon regulates the balance of intestinal microbiota and cellular immunity, and further suppresses the development of inflammatory bowel diseases.

肠道免疫系统必须承担双重任务;该系统应该对抗入侵的病原体，同时，该系统应该对肠道微生物群或食物成分具有耐受性。Dectin-1是真菌细胞壁中表达的β-葡聚糖的受体，并激活免疫系统以防止感染。由于β-葡聚糖广泛存在于各种食物和肠道微生物群中，我们研究了Dectin-1信号传导对肠道免疫的影响。我们发现Dectin-1缺陷小鼠对葡聚糖硫酸钠诱导的结肠炎（一种炎症性肠病模型）是难治的，这是由于结肠中一种革兰氏阳性细菌的扩增与T细胞亚群的再修饰相关。此外，口服海藻衍生的Dectin-1拮抗剂抑制结肠固有层细胞中促炎细胞因子的产生并抑制结肠炎的发展。这些观察结果表明，抑制结肠中的Dectin-1信号传导调节肠道微生物群和细胞免疫的平衡，并进一步抑制炎症性肠病的发展。

项目成果

腸管細菌感染防御におけるβグルカン/Dectin-1シグナルの役割。

β-葡聚糖/Dectin-1 信号在防御肠道细菌感染中的作用。

• 发表时间: 2011
• 作者: 角木 基彦;唐 策;岩倉 洋一郎
• 通讯作者: 岩倉 洋一郎

IL-23 in colitis: Targeting the progenitors.

结肠炎中的 IL-23：针对祖细胞。

• 发表时间: 2012
• 期刊: Immunity
• 影响因子: 32.4
• 作者: Ce;T.
• 通讯作者: T.

IL-17F, rather than IL-17A promotes CD4^+ T cell activation and Th-1-type immunity

IL-17F（而非 IL-17A）促进 CD4^ T 细胞活化和 Th-1 型免疫

• 发表时间: 2011
• 作者: Hasegawa;K.;Umemura;M.;柳本隼人;Misa Okabe;I.Yasuda;Ce Tang
• 通讯作者: Ce Tang

Dectin-1 signaling promotes DSS-induced colitis in a microflora dependent manner

Dectin-1 信号传导以微生物依赖的方式促进 DSS 诱导的结肠炎

• 发表时间: 2011
• 作者: Tanikawa;A.;Umemura;M.;小宮木代良;Tomonori Kamiya
• 通讯作者: Tomonori Kamiya

炎症性大腸炎の病態形成におけるDectin-1の新規の役割解析

Dectin-1在炎症性肠病发病机制中的新作用分析

• 发表时间: 2013
• 作者: 唐策;神谷知憲;角木基彦;大島健志朗;服部正平;岩倉洋一郎
• 通讯作者: 岩倉洋一郎