Intranasal dendritic cell vaccine for asthma using induction of immune tolerance

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K17671
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Furuhashi Kazuki 浜松医科大学, 医学部附属病院, 助教 (70759935)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 肺樹状細胞 / 免疫寛容原性樹状細胞 / 気管支喘息 / 制御性T細胞 / C型レクチン受容体

Outline of Final Research Achievements

Regarding the major subsets of lung dendritic cells, cDC1 and cDC2, we found that they could be subdivided into subsets based on differences in the expression of surface antigens of cDC2 that increased after OVA priming. CLEC10A+ cDC2 induced more efficiency to Treg and had higher antigen phagocytosis capacity than CLEC10A- cDC2. Furthermore, IL-2 production, essential for Treg maintenance, was higher in the CLEC10A+ cDC2 assay. RNA-seq analysis of cDC2 subsets classified by CLEC10A expression revealed that CLEC10A+ cDC2 had higher RNA expression of transcription factors associated with cDC2 differentiation, co-stimulatory molecules, and most C-type lectin receptors.

Free Research Field

呼吸器内科学

Academic Significance and Societal Importance of the Research Achievements

肺における樹状細胞の中で免疫寛容原性樹状細胞のサブセットを同定することは、アレルゲン免疫療法における免疫寛容メカニズムの解明につながり、さらにはこの樹状細胞サブセットを用いて抗原特異的な免疫寛容を誘導し、喘息等のアレルギー疾患の寛解を目指す研究やワクチン開発につながる。本研究の成果により、C型レクチン受容体であるCLEC10A陽性cDC2は、肺において抗原貪食能が高く、最も効率的にTregを誘導するサブセットであるとが判明し、免疫寛容原性樹状細胞のサブセットの一つと考えられ、今後の喘息に対する免疫寛容誘導を利用した樹状細胞ワクチンを開発するための基盤となる知見を得ることができた。