Understanding of the mechanism underlying the tissue-specific differentiation of high endothelial venule endothelial cells

高内皮微静脉（HEV）是在淋巴结和派尔集合淋巴结中特异性发现的血管。尽管HEV表达介导淋巴细胞穿过高壁内皮细胞（HEV-EC）的特异性趋化因子/粘附分子，但调节HEV的发展和维持独特性质的机制仍不清楚。我们对新生小鼠肠系膜淋巴结中HEV-EC和non-HEV -EC进行了微阵列和真实的实时定量PCR分析，并鉴定了五种转录因子，它们在发育中的HEV-EC中的表达量是non-HEV -EC的50倍以上。通过免疫组化分析，我们发现其中一个在E17.5至出生日期间在相当大比例的淋巴结血管内皮细胞核中显示限制性表达模式，这在时间上对应于HEV-EC的发展。该转录因子基因敲除小鼠表现出几个HEV相关基因的表达降低，暗示该基因对HEV-EC分化的功能贡献。

The high endothelial venules (HEVs) are blood vessels specifically found in lymph nodes and Peyer ’ s patches. Although HEVs express specific chemokines/adhesion molecules which mediate lymphocyte t rafficking across the high-walled endothelial cells (HEV -ECs), the mechanism regulating HEVs’ development and maintenance of the unique properties remain unclear. We performed microarray and real -time quantitative PCR analyses of HEV -ECs and non-HEV -ECs inneonatal mice mesenteric LNs, and identified five transcription factors which are over fifty times more abundantly expressed in developing HEV -ECs than in non-HEV -ECs. By immunohistochemical analysis, we found that one of them showed a restricted expression pattern in the nucleus of ECs of a substantial proportion of blood vessels oflymph nodes from E17.5 to the date of birth, which corresponds temporally to HEV -EC development. The gene knockout mice of this transcription factor showed reduced expression of several HEV -associated genes, implying the functionalcontribution of this gene to HEV -EC differentiation.