Functional analyses of dendritic subsets in immune regulation
| Project/Area Number |
16390116
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Kyoto University |
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Principal Investigator |
INABA Kayo Kyoto University, Graduate School of Biostudies, Dept.Animal Dev.Physiol., Professor, 生命科学研究科, 教授 (00115792)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥15,000,000 (Direct Cost: ¥15,000,000)
Fiscal Year 2005: ¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 2004: ¥8,700,000 (Direct Cost: ¥8,700,000)
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| Keywords | dendritic cells / subset / immune regulation / cytokines / type I interferon / cell differentiation / 分化 / 表現型 / ランゲルハンス細胞 / 移動能 / 接触性過敏応答 / 真皮樹状細胞 |
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| Research Abstract |
In this project, we examined functional differences of endocytoic conventional dendritic cells (DCs) with type I interferon-producing plasmacyotoid preDCs (P-preDCs) in immune regulations in terms of cytokine production, T cell activation, and expansion of regulatory T cells. The following results were obtained.
1)Ly49Q is a member of the Ly49 family that is expressed on Gr-1^+ cells, but not on NK and NKT cells. Conventional DCs were found to be negative for Ly49Q, while bone marrow-derived DCs expressed at low level and upregulated by IFN. On the other hand, Ly49Q was expressed on CD11c^+B220^+Gr-1^+P-preDCs in peripheral lymphoid tissues. However, the expression level on P-preDCs were variable in bone marrow. This was ascribed to the difference in differentiation stage of P-preDCs, since Ly49Q was expressed spontaneously upon culture and Ly49Q^+P-preDCs produced larger amounts of IFN-α/β,IL-6 and IL-12 by CpG-ODN.
2)CD25^+CD4^+ regulatory or suppressor Tcells (Tregs) is known to maintain immunological self-tolerance, preventing autoimmunity. Previously we have shown that Tregs proliferate and retain their antigen-dependent suppressive functions when the APCs are antigen-loaded mature dendritic cells (DCs). Using allogeneic polyclonal Tregs, DCs were demonstrated to effectively sustain expression of Foxp3 in Tregs and to be potent for the expansion of alloantigen-specific Tregs in the presence of IL-2. Moreover, those expanded Tregs were efficient to suppressed GvHD induced by CD25- CD4- T cells.
3)We generated mice that harbor a targeted insertion of a primate DTR in the Langerin locus. LCs were effectively and selectively ablated in adult Langerin-DTR mice within 24 h after injection of DT. Reconstitution of the epidermal LC compartment in the steady state took at least 4 wk. Functional analysis of LC-depleted mice revealed that dermal DCs were able to mediate a cutaneous CHS response.
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Report
(3 results)
Research Products
(47 results)
