2012 Fiscal Year Final Research Report
Establishment of a novel immunoregulatory system by enrichment of tolerogenic DCs in donor cornea
| Project/Area Number |
23659821
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Ophthalmology
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| Research Institution | Tokyo Medical University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
HATTORI Takaaki 東京医科大学, 医学部, 講師 (20408173)
USUI Yoshihiko 東京医科大学, 医学部, 講師 (50408142)
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| Project Period (FY) |
2011 – 2012
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| Keywords | 角膜移植 / 制御性樹状細胞 / 拒絶反応 |
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| Research Abstract |
Significant interest has been focused on the use of ex vivo manipulated dendritic cells (DCs) to optimally induce transplant tolerance and promote allograft survival. Though it is understood that donor-derived tolerogenic DCs suppress the direct pathway of allosensitization, whether such DCs can similarly suppress the indirect pathway remains unclear. We therefore utilized the murine model of corneal transplantation to address this, as these allografts are rejected in an indirect pathway dominant fashion. Interestingly, recipients administered with donor bone marrow derived regulatory DCs (DCregs) generated via culturing with GMCSF, IL-10 and TGF-b1, significantly prolonged survival of corneal allografts. We conclude that donor derived tolerogenic DCs significantly suppress the indirect pathway, thereby identifying a novel regulatory mechanism for these cells in transplantation.
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