Detection of human TIM-4 on autoimmune and allergic diseases

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09924
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Juntendo University
• Principal Investigator: Akiba Hisaya 順天堂大学, 医学(系)研究科(研究院), 准教授 (60338316)
• Co-Investigator(Renkei-kenkyūsha): HARADA norihiro 順天堂大学, 医学部, 准教授 (10465065) ; ABE yoshiyuki 順天堂大学, 医学部, 助教 (10647027)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 免疫 / アレルギー / ぜんそく / 炎症 / 診断薬

Outline of Final Research Achievements

T cell immunoglobulin and mucin domain (TIM)-4 plays essential roles in macrophage homeostasis. We have previously detected a soluble form of the extracellular domain of TIM-4 (sTIM-4) generated by proteolytic cleavage of mouse macrophages. sTIM-4 induced proinflammatory cytokine production by naive and IgE-stimulated mast cells. Thus, we measured the concentrations of sTIM-4 in patients with asthma in evaluated 125 adult patients with mild to severe asthma. The serum sTIM-4 levels were significantly higher in the asthmatic patients with step 5 treatment by Global Initiative for Asthma (GINA) as compared with the patients with GINA step 1 to 4 treatment. The data suggest that serum sTIM-4 may be associated with asthma severity and may have the potential to be used as biomarker in asthma.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

遊離型TIM-4は多種の炎症性サイトカイン産生の誘導に働く。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示す患者さんの治療に繋がると考えている。また抗TIM-4抗体による抗炎症作用は、喘息に留まらず、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る。また遊離型TIM-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。