Identification of new macrophages subset expressed nicotinic receptor and those function in intestinal immunity

2016 Fiscal Year Final Research Report

• Project/Area Number: 24248050
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Basic veterinary science/Basic zootechnical science
• Research Institution: The University of Tokyo
• Principal Investigator: Hori Masatoshi 東京大学, 大学院農学生命科学研究科(農学部), 准教授 (70211547)
• Co-Investigator(Kenkyū-buntansha): 藤澤 正彦 日本獣医生命科学大学, 獣医学部, 講師 (10508873) ; 堀口 和秀 福井大学, 医学部, 准教授 (20377451) ; 道下 正貴 日本獣医生命科学大学, 獣医学部, 講師 (50434147)
• Co-Investigator(Renkei-kenkyūsha): MOMOTANI Eiichi 独立行政法人農業, 食品産業技術総合研究機構, 上席研究員 (50355145) ; TAJIMA Tsuyoshi 日本獣医生命科学大学, 獣医学部, 助教 (60508878)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Keywords: α７ニコチン様アセチルコリン受容体 / ムスカリン２アセチルコリン受容体 / セロトニン４受容体 / モサプリド / 抗炎症作用 / 術後イレウス / マクロファージ / 好中球

Outline of Final Research Achievements

We found that local anti-inflammatory signaling via 5-HT4R of myenteric motor neuron are existing in postoperative ileus model, then try to identify the detailed mechanisms. Myenteric motor neurons release ACh via 5-HT4R activation. The released ACh can activate smooth muscle cells resulted induction of gastroprokinetic action in healthy condition. In contrast, in inflamed ileum, the released ACh can activate α7nAChR possibly on resident macrophages in small intestine which in turn inhibit macrophages infiltration. Whereas ACh can also stimulate M2 type muscarinic AChR (M2AChR) resulted in inhibition of neutrophil infiltration.
In conclusion, we for the first time found that there are neuronal anti-inflammatory pathway in small intestine through two type of AChRs. One is α7nAChR activation to inbibit macrophages infiltration, the other is M2AChR activation to inhibit neutrophils infiltration.

Free Research Field

獣医薬理学