Analysis of immune mechanisms common to ulcerative colitis and primary sclerosing cholangitis to elucidate the mechanisms of disease formation.

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K16979
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Chiba University
• Principal Investigator: Ohta Yuki 千葉大学, 医学部附属病院, 医員 (80831510)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 潰瘍性大腸炎 / 原発性硬化性胆管炎 / CD4+T細胞

Outline of Final Research Achievements

Ulcerative colitis (UC) is a disease of unknown cause in which inflammation occurs primarily in the intestinal tract. UC can lead to a variety of extraintestinal manifestations that worsen daily life and prognosis. Primary sclerosing cholangitis (PSC) is one of the extraintestinal manifestations of UC and is a chronic, progressive, bile duct-destroying disease of unknown cause. The purpose of this study is to elucidate the pathogenesis of this disease using CD4+ T cells, which are commonly involved in the immunokinetics of not only UC and PSC, but also PSC complicated UC. Gene expression profiling of peripheral blood CD4+ T cells from UC, PSC, PSC-merged UC and healthy subjects was performed.
Variable expression of disease-specific immune-related molecules was observed in CD4+ T cells from UC and PSC, and both features were observed in PSC-associated UC.

Free Research Field

消化器内科

Academic Significance and Societal Importance of the Research Achievements

潰瘍性大腸炎(UC)と原発性硬化性胆管炎(PSC)はいずれも原因不明の難病であり、両疾患の合併例はそれぞれの単独例よりも生命予後が悪い。本研究ではUC、PSCおよびPSC合併UCに共通して免疫動態に関わるCD4+T細胞に注目し、その遺伝子発現プロファイリングを行った。UCとPSCのCD4+T細胞では疾患特異的な免疫関連分子の発現変動が見られ、PSC合併UCではその両者の特徴が認められた。このことから疾患特異性の高い新規バイオマーカーを探索し、特にPSC合併UCを早期診断し生命予後の改善に寄与できる可能性がある。