Functional analyses of dendritic subsets in immune regulation

树突亚群在免疫调节中的功能分析

基本信息

批准号：
16390116
负责人：
INABA Kayo
金额：
$ 9.6万
依托单位：
Kyoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

项目摘要

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.

在该项目中，我们在免疫法规中检查了II产生的纤溶酶DC（P-PREDCS）在细胞因子的产生，T细胞激活和调节剂的扩展方面，检查了内吞章节章节细胞（DC）的功能差异。 1）LY49Q是在GR-1^+细胞上表达的LY49家族的成员。对培养物和REDC表示的肾脏表达产生了更大量的IFN-α/β，IL-6和IL-12的cpg-odn.2）当我们表现出允许的耐受性和保留依赖性抑制功能时是抗原载的成熟树突状细胞（DC），在同种抗原特异性的Treg中有效，在存在IL-2的情况下。 3）在注射DT后24小时内，我们在成年的Langerin-DTR小鼠中产生了塔伯（Tarbor）的靶向插入。小鼠能够介导皮肤CHS反应。

项目成果

期刊论文数量（47）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Development of murine plasmacytoid dendritic cells defined by increased expression of an inhibitory NK receptor, Ly49Q

DOI：
10.4049/jimmunol.174.11.6657
发表时间：
2005-06-01
期刊：
JOURNAL OF IMMUNOLOGY
影响因子：
4.4
作者：
Omatsu, Y;Iyoda, T;Inaba, K
通讯作者：
Inaba, K

Functional comparison of the mouse DC-SIGN, SIGNR1, SIGNR3 and Langerin, C-type lectins.

DOI：
10.1093/intimm/dxh084
发表时间：
2004-06
期刊：
International immunology
影响因子：
4.4
作者：
K. Takahara;Yusuke Yashima;Y. Omatsu;H. Yoshida;Y. Kimura;Young‐Sun Kang;R. Steinman;Chae Gyu Park;K. Inaba
通讯作者：
K. Takahara;Yusuke Yashima;Y. Omatsu;H. Yoshida;Y. Kimura;Young‐Sun Kang;R. Steinman;Chae Gyu Park;K. Inaba

Association of SIGNR1 with TLR4/MD-2 enhances signal transduction by ecognition of LPS in Gram-negative bacteria.

SIGNR1 与 TLR4/MD-2 的结合可通过革兰氏阴性细菌对 LPS 的识别来增强信号转导。

DOI：
发表时间：
2005
期刊：
Int.Immunol. 17(7)
影响因子：
0
作者：
Hamada;J.;浜田淳一;Sayuri Yamazaki;Kunie Saito;Kunie Saito;Sayuri Yamazaki;Kunie Saito;Sayuri Yamazaki;Ralph M.Steinman;Kayo Inaba;Koji Nagaoka;Clare L.Bennett;Yoshiki Omatsu;Takeshi Nakahara;Noriko Toyama-Sorimachi;Takeshi Nakahara;Noriko Toyama-Sorimachi;Omatsu Yoshiki;Clare L.Bennett;Kayo Inaba;Koji Nagaoka
通讯作者：
Koji Nagaoka

Probing Langerhans cell function by their inducible ablation in mice.

通过小鼠中朗格汉斯细胞的诱导消融来探索朗格汉斯细胞的功能。