Involvement of the Enteric Immune System in the Pathogenesis of Enteric Nervous System Abnormalities.

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K17576
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Chiba University
• Principal Investigator: Fumita Takashi 千葉大学, 医学部附属病院, 医員 (60866995)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 腸管神経 / 腸管免疫 / 好酸球 / ILC2 / neuromedinU / GATA

Outline of Final Research Achievements

I Focused on the interuction between enteric nerves and enteric immunity. So, I analyzed the small intestine of Ncx KO mice with enteric hyperinnervation. Eosinophils were significantly increased in the distal small intestinal lamina propria compared to wild-type mice. RT-qPCR of eosinophil-associated cytokines showed a significant increase in IL5 and neuromedinU(nmU). Histological examination also showed increased expression of nmU, and type2 innate lymphoid cell (ILC2) was also increased, suggesting that enteric nerves mobilize ILC2 via nmU, from which IL5 increases, leading to an increase in eosinophils. This suggests that enteric nerves mobilize ILC2 via neuromedin U, from which IL5 is increased and eosinophils are increased in NcxKO mice.
Eosinophils may also play an intestinal protective role, as eosinophil-deficient NcxKO mice showed an increased susceptibility to enterocolitis.

Free Research Field

腸管神経

Academic Significance and Societal Importance of the Research Achievements

腸管神経異常を認める疾患は腸炎が重篤となる傾向にある。しかし自然状態で腸炎を発症している訳ではないため、そこに何かしらかの免疫学的代償機構が働いていると仮説を立て研究を行った。腸管神経増多を呈し腸管運動異常をきたすNcx遺伝子をノックアウトしたマウスは腸炎の感受性亢進を認めているおり、そのマウスを用いて研究を行うと小腸粘膜固有層で好酸球が増加しており、その好酸球を欠損させると腸炎の感受性がさらに亢進したことから好酸球が腸管保護的に働いている可能性を発見した。