Distribution and function of IL-7-producing cells

IL-7产生细胞的分布和功能

基本信息

批准号：
21590531
负责人：
IKUTA Koichi
金额：
$ 3万
依托单位：
Kyoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2009
资助国家：
日本
起止时间：
2009 至 2011
项目状态：
已结题

项目摘要

IL-7 is an essential cytokine for lymphocyte development and survival produced by mesenchymal and epithelial cells in lymphoid organs. However, little is known about the precise nature and distribution of IL-7-expressing cells in vivo. To address this question, we established IL-7-GFP knock-in mice. We found that GFP is expressed in bone marrow stromal cells, thymic epithelial cells(TECs), fibroblastic reticular cells(FRCs) and lymphatic endothelial cells in lymph nodes, and intestinal epithelial cells. After induction of acute colitis with DSS, GFP expression was elevated in the intestinal epithelial cells. Thus, the IL-7-GFP knock-in mouse reveals unreported types of IL-7-expressing cells and provides a powerful tool to analyze the IL-7-niche in the lymphoid organs under physiological and pathological conditions. We next established IL-7-floxed mice and crossed with FoxN1-Cre transgenic(Tg) mice to obtain the conditional knockout mice deficient in IL-7 production from TECs. FoxN1-Cre … More IL-7flox/flox mice showed severely reduced numbers of total andγδT cells in the thymus. These results suggested that IL-7 produced by TECs plays a major role in proliferation, survival, and maturation of thymocytes. In small intestine, cell numbers ofγδIELs were significantly reduced in FoxN1-Cre IL-7flox/flox mice, suggesting that IL-7 produced in the thymus is essential forγδIEL development. Thus, this study presents strong evidence for the thymic originγδIELs. We next crossed IL-7-floxed mice with albumin promoter-driven Cre(Alb-Cre) Tg mice to establish conditional knockout of IL-7 in hepatocytes. We found that NKT and T cells were moderately decreased in adultliver of IL-7f/f Alb-Cre mice and that B cell development was impaired in perinatal liver of IL-7f/f Alb-Cre mice. This study demonstrates that hepatocyte-derived IL-7 plays an indispensable role in maintenance of NKT and T cells in adult liver and development of B cells in fetal liver and suggests that hepatocytes provide a unique IL-7 niche for intrahepatic lymphocytes. Less

IL-7是淋巴细胞和上皮细胞在淋巴机构中产生的淋巴细胞发育和生存的必不可少的细胞因子。但是，对于体内表达IL-7的细胞的精确性质和分布知之甚少。为了解决这个问题，我们建立了IL-7-GFP敲入小鼠。我们发现GFP在淋巴结淋巴结中的骨髓基质细胞，胸腺上皮细胞（TEC），成纤维细胞网状细胞（FRC）和淋巴内皮细胞和肠上皮细胞中表达。用DSS诱导急性结肠炎后，肠上皮细胞中GFP表达升高。这就是IL-7-GFP敲入小鼠揭示了表达IL-7的细胞的未报告类型，并提供了一种强大的工具，可以在物理和病理条件下分析淋巴器官中的IL-7-niche。接下来，我们建立了IL-7 lo烟小鼠，并与FOXN1-CRE转基因（TG）小鼠越过，以获得TEC中IL-7产生缺乏的条件敲除小鼠。 FOXN1-CRE…更多的IL-7flox/Flox小鼠显示胸腺中总和γδT细胞的数量严重减少。这些结果表明，TEC产生的IL-7在胸腺细胞的增殖，存活和成熟中起主要作用。在小肠中，在FOXN1-CRE IL-7FLOX/FLOX小鼠中，细胞数量显着降低，这表明胸腺中产生的IL-7对于γδILE的发育至关重要。这项研究为胸腺起源γδiels提供了有力的证据。接下来，我们与白蛋白启动子驱动的CRE（ALB-CRE）TG小鼠跨越IL-7 lo-lox小鼠，以在肝细胞中建立IL-7的条件敲除。我们发现在IL-7F/F ALB-CRE小鼠的成年基因中，NKT和T细胞适度改善，并且在IL-7F/F ALB-CRE小鼠的围产期肝脏中，B细胞发育受损。这项研究表明，肝细胞衍生的IL-7在成年肝脏中NKT和T细胞的维持中起着必不可少的作用，以及胎儿肝脏中B细胞的发育，并表明肝细胞为肠内淋巴细胞提供了独特的IL-7 nikee。较少的

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Activation of the mouse T cellreceptorγenhancers by STAT5

STAT5 激活小鼠 T 细胞受体γ增强子

DOI：
10.1093/intimm/dxp073
发表时间：
2009
期刊：
Int. Immunol
影响因子：
0
作者：
Tani-ichi;S.;Satake;M.;and Ikuta;K.
通讯作者：
K.

The pre-TCR signal induces transcriptional silencing of the TCRγ locus by reducing the recruitment of STAT5 and Runx to transcriptional enhancers

DOI：
10.1093/intimm/dxr055
发表时间：
2011-09-01
期刊：
INTERNATIONAL IMMUNOLOGY
影响因子：
4.4
作者：
Tani-ichi, Shizue;Satake, Masanobu;Ikuta, Koichi
通讯作者：
Ikuta, Koichi

Essential role of interleukin-17A in the formation of a mycobacterial infection-induced granuloma in the lung

IL-17A 在分枝杆菌感染诱导的肺部肉芽肿形成中的重要作用

DOI：
发表时间：
2010
期刊：
J. Immunol
影响因子：
0
作者：
Okamoto;Y. Y.;Umemura;M.;Yahagi;A.;O' Brien;R. L. Ikuta;K;Kishihara;K.;Hara;H.;Nakae;S.;Iwakura;Y. and Matsuzaki;G.
通讯作者：
G.

腸管上皮内γδT細胞は胸腺に由来する

肠上皮内 γδ T 细胞起源于胸腺