Establishment of the method for efficient induction of human regulatory T cells and tolerogenic dendritic cells and application to therapy

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591464
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Ehime University
• Principal Investigator: HASEGAWA Hitoshi 愛媛大学, 医学(系)研究科(研究院), 准教授 (40164826)
• Co-Investigator(Renkei-kenkyūsha): SUEMORI Koichiro 愛媛大学, 医学部附属病院, 助教 (80571083)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: dendritic cells / regulatory T cells / protein kinase C

Outline of Final Research Achievements

Tolerogenic dendritic cells (tDCs) are a promising tool for cellular therapy for allergy and autoimmunity. From libraries of bioactive lipids, nuclear receptor ligands, and kinase inhibitors, we screened conventional protein kinase C inhibitors (PKCIs) with strong tolerogenic potential. The PKCI-treated DCs had a semi-mature phenotype, showing high production of IL-10, and efficiently induced IL-10-producing T cells and functional Foxp3+ regulatory T cells from naive CD4+ T cells, thus eliciting a strong immunosuppressive function. They also showed CCR7 expression and sufficient capacity for migration toward CCR7 ligands. In addition, PKCI-treated DCs were highly stable when exposed to inflammatory stimuli such as proinflammatory cytokines or LPS. Moreover, PKCI-treated mouse DCs that had properties similar to PKCI-treated human DCs prevented graft-vs-host disease (GVHD) in a murine model of acute GVHD. Conventional PKCI-treated DCs may be useful for tolerance-inducing therapy.

Free Research Field

膠原病・アレルギー内科学