Are changes in the properties of Paneth cells a starting point for inflammatory bowel disease?

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08017
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: University of Occupational and Environmental Health, Japan
• Principal Investigator: Baba Ryoko 産業医科大学, 医学部, 准教授 (90271436)
• Co-Investigator(Kenkyū-buntansha): 森本 景之 産業医科大学, 医学部, 教授 (30335806) ; 國分 啓司 産業医科大学, 医学部, 助教 (00432740) ; 中村 健太 産業医科大学, 医学部, 非常勤医師 (60789692)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 回腸 / 杯細胞 / パネート細胞 / 炎症性腸疾患 / TNF-α / オルガノイド / ヒストンメチル化

Outline of Final Research Achievements

It is becoming clear that the pathology of inflammatory bowel disease (IBD) is closely related to the functional breakdown of the intestinal epithelium. However, the cause of onset is not completely understood. It is known that ectopic appearance of Paneth cells and abnormal Paneth cells occur in IBD. In IBD model mice, immature Paneth cells, unusual secretory granules, and impaired degranulation have been reported. We considered that the Paneth-like cells that appear in IBD are an immature form. In addition, the decrease in goblet cell number and ectopic appearance of Paneth cells in IBD were thought to be due to change in differentiation. In this study, we performed morphological analyzes using developing mouse ileum, IBD model mouse ileum, and ileal organoids. In inflammatory conditions, ileal crypts and Paneth cells showed similar changes in mice and organoids. This suggests that inflammation is associated with Paneth cell differentiation and maturation.

Free Research Field

組織学

Academic Significance and Societal Importance of the Research Achievements

IBDでパネート細胞の異所性出現、異常、杯細胞の減少が、IBDモデルマウスで未熟なパネート細胞、果粒の異常、脱果粒の障害が報告されており、IBDとパネート細胞との関連が推測される。今回、モデル動物回腸やオルガノイド回腸上皮に顕著な障害は見られなかったが、パネート細胞に変化が認められた。炎症の持続や再燃等により小腸にも障害を生じる可能性がある。また、パネート細胞に変化が生じる背景にヒストンメチル化の関与を示すことができた。今後、ヒストンメチル化で発現が変動する遺伝子の解明を目指す。炎症とパネート細胞の形態変化との関連を明らかにすることは、IBD発症の機序解明や予防に繋がると考える。