Distribution and function of IL-7-producing cells

白细胞介素-7是淋巴器官间充质细胞和上皮细胞产生的淋巴细胞发育和存活所必需的细胞因子。然而，对il -7表达细胞在体内的确切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在骨髓基质细胞、胸腺上皮细胞（TECs）、成纤维网状细胞（FRCs）、淋巴结淋巴内皮细胞和肠上皮细胞中表达。DSS诱导急性结肠炎后，肠上皮细胞中GFP表达升高。因此，IL-7-GFP敲入小鼠揭示了未被报道的il -7表达细胞类型，并为分析生理和病理条件下淋巴器官中il -7的生态位提供了有力的工具。接下来，我们建立了IL-7的小鼠，并与FoxN1-Cre转基因（Tg）小鼠杂交，获得了从tec中产生IL-7缺陷的条件敲除小鼠。IL-7flox/flox组小鼠胸腺总t细胞和γδ t细胞数量明显减少。这些结果表明，TECs产生的IL-7在胸腺细胞的增殖、存活和成熟中起重要作用。在小肠中，FoxN1-Cre IL-7flox/flox小鼠的γδ iel细胞数量显著减少，表明胸腺中产生的IL-7对γδ iel的发育至关重要。因此，本研究为胸腺起源γδ iels提供了强有力的证据。接下来，我们将IL-7捆绑小鼠与白蛋白启动子驱动的Cre(Alb-Cre) Tg小鼠杂交，以建立肝细胞中IL-7的条件敲除。我们发现，IL-7f/f Alb-Cre小鼠成年肝脏中NKT和T细胞轻度减少，IL-7f/f Alb-Cre小鼠围产期肝脏中B细胞发育受损。本研究表明，肝细胞来源的IL-7在成人肝脏中NKT和T细胞的维持以及胎儿肝脏中B细胞的发育中起着不可或缺的作用，并表明肝细胞为肝内淋巴细胞提供了独特的IL-7生态位。少

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