Investigation of IL-12/23 pathway in ulcerative colitis

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K15992
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Shimizu Hiromichi 東京医科歯科大学, 統合研究機構, 助教 (00733875)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 潰瘍性大腸炎 / ILー12／23 / 大腸オルガノイド

Outline of Final Research Achievements

Ulcerative colitis is an idiopathic disease which causes chronic inflammation in colon. For the treatment of ulcerative colitis, anti-inflammatory agents are used such as corticosteroid, immune-modulator and biologic agents. Anti-IL-12/23 anti-body is one of biologic agent blocking specific pro-inflammatory IL-12/23 pathway in colonic tissue. IL-12/23 pathway is a proinflammatory cytokine in ulcerative colitis, interacting numerous other pathways to exacerbates colitis. This study, analyzing patient derived colonic tissue, was aiming to find out in which cells IL-12/23 has any effects, how anti-IL-12/23 antibody reduces and blocks proinflammatory response in colonic tissue, and what is the key biomarkers and/or conditions that determine its treatment efficacy. We underwent single-cell RNA analysis on organoids generated from colonic tissue derived from the patients with ulcerative colitis.

Free Research Field

再生医療研究

Academic Significance and Societal Importance of the Research Achievements

潰瘍性大腸炎の治療における分子標的薬は、腸管で炎症を引き起こす複雑なサイトカイン・ネットワークの、特異的な経路を阻害して効果を発揮する。しかし、抗IL-12/23抗体製剤が、どの種類の細胞を標的とし、どのように障害された腸粘膜を治癒するのか、そのメカニズムはよくわかっていない。本研究は、患者の臨床情報と患者由来の組織検体の解析を通じて、分子標的薬のひとつ抗IL-12/23抗体製剤の作用メカニズムの解明と、治療予測因子の同定を試みることで、抗IL-12/23抗体製剤の治療効果予測の解明を目標とした研究である。