2018 Fiscal Year Final Research Report

Molecular understanding of CD26-mediated immune regulatory mechanism and development of novel molecular targeted therapy for the treatment of refractory autoimmune diseases

Research Project

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Project/Area Number	16H05345
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Research Field	Collagenous pathology/Allergology
Research Institution	Juntendo University
Principal Investigator	Morimoto Chikao 順天堂大学, 医学(系)研究科(研究院), 特任教授 (30119028)
Co-Investigator(Kenkyū-buntansha)	岩田哲史順天堂大学, 医学(系)研究科(研究院), 非常勤講師 (00396871) 大沼圭順天堂大学, 医学(系)研究科(研究院), 准教授 (10396872) 波多野良順天堂大学, 医学(系)研究科(研究院), 特任助教 (30638789)
Project Period (FY)	2016-04-01 – 2019-03-31
Keywords	CD26/DPPIV / T細胞 / 共刺激分子 / IL-10 / ヒト免疫 / 免疫チェックポイント分子 / 全身性エリテマトーデス / 悪性胸膜中皮腫
Outline of Final Research Achievements	CD26 is a T cell costimulatory molecule, and plays an important role in the human immune system. We have recently shown that CD26 not only functions in T cell activation, but also may serve as an immune regulator. From our extensive examination, we found that the expression levels of IL-10, LAG3 and BTLA in human CD4 T cells, and those of BTLA in CD8 T cells were markedly enhanced following CD26 costimulation, as compared with CD28 costimulation. However, CD26+LAG3+ or BTLA+ CD4 T cells or CD26+BTLA+ CD8 T cells were hardly found in the peripheral blood of SLE patients or healthy adult volunteers. In contrast, the percentage of immune checkpoint molecules-expressing T cells was prominently increased in the pleural fluid of malignant pleural mesothelioma patients, and we could find CD26+LAG3+ or CD26+BTLA+ T cell subsets in the pleural fluid. The molecular mechanisms how the expression of LAG3 or BTLA is induced following CD26 costimulation are needed to be investigated in the future.
Free Research Field	臨床免疫学
Academic Significance and Societal Importance of the Research Achievements	CD26分子はマウスT細胞では共刺激分子として機能せず、ヒト免疫において重要な分子である。免疫応答の負の制御メカニズムの解明は、自己免疫疾患の発症・悪化の根幹をなす問題であり、また、近年腫瘍免疫の分野においても、免疫応答を負に制御する免疫チェックポイント分子を阻害する免疫チェックポイント阻害薬は新たな治療薬として非常に注目されている。さらに申請者らが開発したヒト化CD26抗体は、悪性胸膜中皮腫に対する第I/II相臨床試験を実施しているところであり、CD26抗体の新たな抗腫瘍作用メカニズムの解明にもつながることが期待される。