Wnt信号通路与胸腺发育

胸腺是人体重要的中枢淋巴器官,是T淋巴细胞分化发育的场所。起源于骨髓的淋巴细胞祖细胞,在胸腺中历经阳性选择和阴性选择后发育为成熟的T细胞,然后通过血液循环参与外周细胞免疫。研究表明,Wnt信号通路广泛存在于胸腺上皮细胞和T细胞,它不但影响胸腺上皮细胞的形态、功能,而且对于维持T细胞前体细胞和后期T细胞的分化发育都很重要。最近研究发现,Wnt信号通路参与了胸腺增龄性萎缩过程的调节,Wnt信号通路的改变可引起上皮网络结构的改变,最终导致胸腺微环境的破坏。因此,研究Wnt信号通路在胸腺发育中的作用,对于探索胸腺增龄性萎缩的调控机制和改善老年人的健康状况有重要意义。     

神经发育中基因调控研究进展

神经发育是一个极其复杂的生物学过程,最近每年都有大量的研究报告,本文将为读者提供几个侧面,以引起我国科学工作者的兴趣。 早期神经发生的有关基因 导致神经原基(neural Primordium)形成的早期神经发生是研究神经细胞分化的合适系统。果蝇神经母细胞在外胚层神经发生区中分离出来是神经发育的开端。这些神经母细胞将     

胸腺细胞分化发育的凋亡调控

胸腺细胞在胸腺内的发育过程经历了TCR基因重排与表达、阳性选择和阴性选择三个主要过程。凋亡,又称程序性细胞死亡,在胸腺细胞发育过程贯穿始终,因此研究胸腺内T细胞发育过程中的凋亡对揭示胸腺选择作用和中枢耐受形成机制有重要意义。本文就胸腺细胞在胸腺内发育过程中凋亡的发生及其调控作一综述。     

胸腺增龄性萎缩分子机制研究进展

胸腺是哺乳动物重要的中枢免疫器官,是决定和制约免疫系统老化的关键.胸腺作为T 细胞分化、发育、成熟重要场所,随着增龄表现出明显萎缩的现象进而影响到T细胞的发育、增殖和输出,从而造成外周淋巴组织中T细胞的质与量的异常,这样就不可避免地降低了免疫系统对外来的抗原应答性,导致病原体清除延迟,增加了老年人罹患癌症、自身免疫性疾...     

脊椎动物中枢神经系统发育相关基因的级联调控

脊椎动物的中枢神经系统是一系列在组成上高度复杂的细胞构成的。它的形成经历了一个极其复杂的发育分化过程。这一过程受到了多种基因的级联调控（ＣａｓｃａｄｅＲｅｇｕｌａｔｉｏｎ）。参与这一级联调控网络的基因不仅包括了同源盒基因等编码转录因子的基因，其它一...     

胸腺T细胞分化发育的神经内分泌调控

胸腺对机体免疫功能起着不可替代的作用,胸腺细胞的分化发育成熟过程接受神经内分泌调控,神经内分泌影响胸腺细胞增殖。激素和神经肽受体在胸腺细胞上表达,参与调控胸腺内分泌功能,本文对神经内分泌对胸腺细胞分化发育的影响及其可能的机制进行了讨论。     

B淋巴细胞发育的基因调控

B淋巴细胞通过形成抗原特异性免疫球蛋白在免疫过程中具有重要的作用。哺乳类动物B细胞分化最早部位是在胚胎早期的卵黄囊, 随后发生于胎肝, 在个体出生后进一步在骨髓中发育, 在外周淋巴器官中成熟。成熟B细胞定居于周围淋巴组织, 如淋巴结皮质浅层和脾的红髓及白髓的淋巴小结内。成熟的B细胞在抗原或者其他配体的刺激下形成分泌抗体的浆细胞, 执行体液免疫 [1]。对于B细胞发生, 基因调控有重要作用, 现对其发生过程以及涉及的几种主要调控基因综述如下。1　造血干细胞(hematopoieticstemcells)造血干细胞由处于静息状态的、自我更新…     

miR-194 在增龄性胸腺萎缩中的表达及靶基因研究

目的:检测增龄性胸腺萎缩过程中miR-194 与PTPN12 的表达水平变化,并分析二者相互作用,阐明其中的分子调节机制。方法:选用C57BL/6 小鼠,分为4 组:1 月龄组、6 月龄组、10 月龄组和19 月龄组,每组6 只,雌雄各半。麻醉后取出胸腺组织,用CD45 抗体与LS 柱吸附洗脱,筛选出胸腺上皮细胞。实时荧光定量PCR 与Western blot 方法检测随年龄增长,胸腺上皮细胞中miR-194 与PTPN12 基因的表达变化趋势。体外实验共转染miR-194 与PTPN12 荧光素酶报告载体到HEK293 细胞内,分别于24、48 h 后检测自发荧光值。结果:随月龄增长,miR-194 表达出现下调趋势(P<0.05),而PTPN12 基因表达出现上调趋势(P<0.05),且二者呈负相关性(P<0.05)。体外荧光素酶报告基因结果显示,miR=194 与PTPN12 基因3’UTR 区域发生直接作用,并在48 h 结合效率最高。结论:PTPN12 是miR-194 靶基因之一,参与了增龄性胸腺萎缩过程,是调节胸腺上皮细胞功能的重要因子。     

胸腺增龄性萎缩的机理及其逆转

由第Ⅲ、Ⅳ对咽囊胚层发育而来的胸腺是重要的中枢免疫器官、Ｔ细胞分化成熟场所。动物在出生后胸腺的重量均与年龄增长呈负相关[1] 。成年Ｓｐｒａｇｕｅ Ｄａｗｌｅｙ大鼠胸腺结构光镜和电镜观察见坏死和纤维化的区域随年龄增长而逐渐扩大 ,皮质区域进行性缩小 ,胸腺细胞体积     

胚胎胸腺细胞在体外胚胎胸腺器官培养中的发育研究

体外可调控的Ｔ细胞培养系统的建立 ,为研究Ｔ细胞发育及Ｔ细胞和基质细胞的作用提供了很好的实验模型 ,如胸腺或基质细胞的分离培养和胚胎胸腺器官培养 (ＦＴＯＣ) 〔1〕。近年来研究表明 ,长期体外培养的胸腺基质细胞 ,由于表型的变化如ＭＨＣⅡ类分子丢失 ,而失去了支持Ｔ细胞发育的能力 ,其应用受到限制。而ＦＴＯＣ保持了体内胸腺的三维空间结构、恒定的细胞表型、适宜的细胞 细胞间的相互作用、基质细胞分泌的多种细胞因子 ,为研究Ｔ细胞的发育提供了更符合生理的胸腺微环境。研究表明 ,ＦＴＯＣ是目前唯一的能支持前体Ｔ细胞完成整…     

Epithelial-cell architecture during involution of the human thymus

One hundred thymus glands were assessed histologically as to their degree of involution. Epithelial cells were demonstrated by an immunoperoxidase method using a monoclonal antibody against cytokeratin. The distribution of these cells was studied in the medulla, the cortico-medullary junction, the cortical parenchyma and the subcapsular cortex. As involution proceeds, the loss of cells from the thymus is almost totally confined to the lymphoid-cell elements. The architecture of the epithelial-cell network remains largely intact although there is extensive collapse of the structure due to the loss of the intervening lymphocytes. Even when involution is apparently complete; sheets of epithelial cells can be demonstrated in the thymic remnant.     

成血管血液干细胞特化形成相关基因的研究进展

在鼠和人的胚胎发生过程中,血细胞紧邻内皮细胞发育.在卵黄囊血岛、胚内腹侧中胚层-副主动脉层/主动脉性腺-中肾(para aortic splanchnopleura/aorta gonad mesonephros,PAS/AGM)     

Elevated intrathymic sphingosine-1-phosphate promotes thymus involution during sepsis

Sepsis mouse models revealed thymus atrophy, characterised by decreased thymus weight and loss of thymocytes due to apoptosis. Mice suffered from lymphopenia, a lack of T cells in the periphery, which attenuates their ability to fight against recurring and secondary infections during sepsis progression. Key players in thymus atrophy are IL-6, which is directly involved in thymus involution, and the sphingosine-1-phosphate − sphingosine-1-phosphate receptor 1 signaling, influencing thymocytes emigration. In healthy individuals a sphingosine-1-phosphate (S1P) gradient from lymphoid organs to the circulatory system serves as signal for mature T cell egress. In the present study we investigated, whether inhibition of S1P generation improves thymus involution. In sepsis, induced by cecal ligation and puncture (CLP), S1P in the thymus increased, while it decreased in serum, thus disrupting the naturally occurring S1P gradient. As a potential source of S1P we identified increased numbers of apoptotic cells in the thymic cortex of septic mice. Pharmacological inhibition of the S1P generating sphingosine kinases, by 4- [[4-(4-Chlorophenyl)-2-thiazolyl]amino]phenol (SK I–II), administered directly following CLP, prevented thymus atrophy. This was reflected by lymphocytosis, diminished apoptosis, decreased IL-6 expression, and an unaltered thymus weight. In addition SK I-II-treatment preserved the S1P balance and prevented S1P-dependent internalization of the sphingosine-1-phosphate receptor 1. Our data suggest that inhibition of sphingosine kinase and thus, S1P generation during sepsis restores thymic T cell egress, which might improve septic outcome.     

Limited development capacity of the earliest embryonic murine thymus

Previous studies have demonstrated that murine thymus separates from the pharynx during 11.5–12 days of gestation, and that the proliferation of thymic cells starts at this age. We characterized embryonic day 12 thymus in terms of the surface phenotype of the thymus cells, the function of the lobe in supporting T cell development in organ culture, and the precursor activity of the thymus cells in a mixed culture with deoxyguanosine-treated lobes. The phenotype of the major population of embryonic day 12 thymus cells was HSA⁺, CD44⁺, c-kit⁺, Thy-1^?, CD25^?, CD4^?, CD8^?, TcR^?, and Sca-1^?. In organ culture of embryonic day 12 thymus lobes, most of the lobes did not develop well and failed to generate CD4⁺CD8⁺, CD4⁺CD8^?, or CD4^?CD8⁺ cells, even when embryonic day 14 thymus cells were added. However, thymus cells on embryonic day 12 contained T cell precursors that developed into mature T cells in co-culture with deoxyguanosine-treated fetal thymic lobes. The majority of the stromal cells in deoxyguanosine-treated embryonic day 14 thymus lobes expressed the surface molecules I-A and H-2D, whereas these cells in embryonic day 12 thymus lobes were negative for these surface molecules. Thus, our findings suggest that the embryonic day 12 thymus lobe contains T cell precursors, but that the undeveloped thymic stromal cells are insufficient to support full T cell development.     

STZ诱导小鼠糖尿病模型中胸腺异位基因表达的研究

目的 探讨胸腺异位基因表达与自身耐受及自身免疫病的相互关系。方法 采用链脲佐菌素（STZ）诱导昆明小鼠糖尿病作为动物模型；利用RT-PCR方法检测小鼠胸腺异位基因表达水平。结果 1型糖尿病（IDDM）小鼠胸腺的异位基因表达水平明显低于对照组小鼠。结论 异位基因表达水平降低可能是引起IDDM的重要原因。