Immune regulation on autoimmune and allergic diseases by the TIM family molecules

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293087
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Juntendo University
• Principal Investigator: Okumura Ko 順天堂大学, 医学部, 教授 (50009700)
• Co-Investigator(Kenkyū-buntansha): 秋葉 久弥 順天堂大学, 医学(系)研究科(研究院), 准教授 (60338316)
• Co-Investigator(Renkei-kenkyūsha): KOJIMA Yuko 順天堂大学, 医学研究科, 助教 (60231312)
• Research Collaborator: KAMACHI Fumitaka ; HARADA Norihiro ; ABE Yoshiyuki ; ISSHIKI Takuma
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 免疫学 / 自己免疫疾患 / アレルギー疾患 / 炎症

Outline of Final Research Achievements

In this study, we investigated the effects of anti-TIM-4 mAb in a murine model of mast cell-dependent anaphylaxis and lung inflammation. Accumulation of eosinophils and production of Th2 cytokines in the lung were significantly reduced in the anti-TIM-4-treated mice. We confirmed that TIM-4 through proteolytic cleavage of cell surface TIM-4. Moreover, TIM-4 regulated the cytokine production, but not degranulation, by mast cells through the interaction with leukocyte mono-Ig-like receptor 5 (LMIR5) and protein X. Taken together, it is possible that TIM-4 can be an appropriate target for the therapeutic treatment and/or the diagnostic marker of allergic diseases.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

現在、TNF-αなど個々の炎症性サイトカインを標的にした抗体医薬品は実用されているが、多種の炎症性サイトカイン産生を総合的に根本から抑制することが可能になれば、個々の抗サイトカイン抗体療法に抵抗性を持つ患者さんの治療に繋がる。また抗TIM-4抗体による抗炎症作用は、関節炎に留まらず、他の難治性慢性炎症疾患の新たな治療ターゲット分子になる可能性があり、またsTIM-4は補助診断あるいは治療効果や予後予測に際して有用なバイオマーカーになる可能性がある。