Overexpression of IL-6 and IL-12 may contribute to the pathogenesis of TRIM22 deficiency -related intestinal inflammation

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K16852
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Kyoto University
• Principal Investigator: Hiejima Eitaro 京都大学, 医学研究科, 特定病院助教 (60773520)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 小児期発症 / 炎症性腸疾患 / TRIM22 / IL-6 / IL-12

Outline of Final Research Achievements

Recently, whole exome sequencing analysis identified homozygous or heterozygous TRIM22 variants in patients with very early onset inflammatory bowel disease (VEO-IBD) which is defined as IBD presenting before 6 years of age. However, the precise mechanism of the intestinal inflammation in TRIM22 deficiency has not been elucidated. We found TRIM22 may be associated with expression of mole cule ‘X’ which has regulatory effect on IL-6 and IL-12 production. Also, we showed ubiquitination of molecule ‘X’ in the presence of TRIM22 may be associated with stabilization of molecule ‘X’.We are conducting more investigation to clarify the role of TRIM22 in regulation of intestinal inflammation.

Free Research Field

小児肝臓消化器

Academic Significance and Societal Importance of the Research Achievements

難治性の小児期早期発症の炎症性腸疾患（IBD）は、未知の単一遺伝子疾患が多く存在していると考えられる。疾患特異的な治療法確立のためには、遺伝子変異による腸管炎症発症の病態解明が不可欠である。我々はTRIM22遺伝子異常による腸管炎症の発症にIL-6, IL-12産生制御異常が関与している可能性を示唆する結果を得たが、更に腸管炎症の分子機序を明らかにできれば、TRIM22遺伝子異常によるIBDのみならず、IL-6或いはIL-12産生異常を起こす小児期早期発症のIBDの病態解明と新規治療開発の基盤構築につながると期待される。