Functional abnormalities of macrophages based on the alteration of iron metabolism and their involvement in the pathogenesis of inflammatory bowel disease

• Project/Area Number: 18K07969
• 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: Kyorin University (2019-2020); Kyoto University (2018)
• Principal Investigator: Matsuura Minoru 杏林大学, 医学部, 准教授 (30402910)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 炎症性腸疾患 / 鉄代謝 / マクロファージ / 鉄動態

Outline of Final Research Achievements

IL-10 KO mice showed abnormal iron metabolism with the development of intestinal inflammation. IL-10 mice were fed normal or restricted iron diet. Histologic inflammation of colonic tissues in the restricted iron diet group was ameliorated compared to normal iron diet group. IL-10 KO mice fed restricted iron diet revealed a significantly lower amount of intracellular iron and a higher proportion of CD206 positive cells in intestinal macrophages compared to that of the normal iron diet group. The production of inflammatory cytokines from J774 cells chelated intracellular iron was significantly lower than that of the control group. Our findings suggest that the alteration of iron metabolism in vivo with the development of chronic intestinal inflammation is involved in the pathogenesis of IBD by enhancing macrophage function due to increased intracellular iron content.

Academic Significance and Societal Importance of the Research Achievements

鉄がIBDの病態に関与するメカニズムとして酸化ストレスや腸内細菌を介した機序が主に報告されている。一方、生体内の鉄代謝調節の中心的分子であるhepcidinとIBDに関する報告は既にいくつか存在するが、そのほとんどは疾患活動性とhepcidin発現の関連性や炎症性貧血に関するものである。このようにIBD患者における生体内の鉄代謝異常やその病態への関与については未だ報告がなく、本研究は鉄がIBDの病態に関与する新たなメカニズムを解明する上での糸口になる可能性がある。