| Project/Area Number |
23791985
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Ophthalmology
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| Research Institution | Tottori University |
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Principal Investigator |
KOMATSU Naoki 鳥取大学, 医学部附属病院, 医員 (50599925)
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| Research Collaborator |
MIYAZAKI Dai 鳥取大学, 医学部附属病院, 講師 (30346358)
KANDORI Michiko 鳥取大学, 医学部附属病院, 医員
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| Project Period (FY) |
2011 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2011: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | 角膜内皮 / 抗原提示 / IDO1 / TLR3 / TLR9 / 免疫特権 / 角膜 |
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| Research Abstract |
The anterior chamber of the eye is a canonical immune privileged site. Corneal endothelial cells line the inner walls of the anterior chamber, and contribute to establishment of ACAID. We analyzed how corneal endothelial cells may exert immune regulatory roles. Herpes simplex virus type 1 (HSV-1) is one of the leading corneal pathogens and cause of blinding endothelial dysfunction. Therefore, we firstdetermined whether HSV-1 can modulate the host immune responses. We examined the transcriptional responses of human corneal endothelial cells (HCEn). Network analysis showed that Indoleamine 2,3-dioxygenase 1 (IDO1) was induced and positioned in the primary network with antigen presenting function. When HCEn cells were examined for antigen presentation, HSV-primed HCEn cells stimulated the proliferation of allogeneic CD4+ T cells as a recall response, which was manifested by IL-10 secretion. Co-cultures of CD4+ T cells with HSV-primed HCEn cells led to the differentiation of CD4+T cells into regulatory T cells (Tregs) as shown by inhibition of the recall response of CD4+. The role of IDO1 was examined by determining whether it functionally modulated the immune response by inducing Treg. When IDO1 was over-expressed in HCEn cells, diversion to Treg was promoted by HCEn cells, and IDO1 inhibition of HCEn cells by siRNA reduced the HCEn-mediated Treg diversion. Corneal endothelial cells were shown to exert immune regulatory role in MHC class II restricted manner via induction of IDO1 upon viral infection.
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