Sultana Dil Afroz, Tomita Shuhei, Hamada Michito, Iwanaga Yasuyuki, Kitahama Yuki, Khang Nguyen Van, Hirai Shuichi, Ohigashi Izumi, Nitta Sachiko, Amagai Takashi, Takahashi Satoru, Takahama Yousuke
Division of Experimental Immunology, Institute for Genome Research, University of Tokushima, Tokushima, Japan.
Blood. 2009 Mar 26;113(13):2976-87. doi: 10.1182/blood-2008-06-164921. Epub 2009 Jan 22.
The thymus provides a microenvironment that induces the differentiation of T-progenitor cells into functional T cells and that establishes a diverse yet self-tolerant T-cell repertoire. However, the mechanisms that lead to the development of the thymus are incompletely understood. We report herein the results of screening for genes that are expressed in the third pharyngeal pouch, which contains thymic primordium. Polymerase chain reaction (PCR)-based cDNA subtraction screening for genes expressed in microdissected tissues of the third pharyngeal pouch rather than the second pharyngeal arch yielded one transcription factor, MafB, which was predominantly expressed in CD45(-)IA(-)PDGFRalpha(+) mesenchymal cells and was detectable even in the third pharyngeal pouch of FoxN1-deficient nude mice. Interestingly, the number of CD45(+) cells that initially accumulated in the embryonic thymus was significantly decreased in MafB-deficient mice. Alterations of gene expression in the embryonic thymi of MafB-deficient mice included the reduced expression of Wnt3 and BMP4 in mesenchymal cells and of CCL21 and CCL25 in epithelial cells. These results suggest that MafB expressed in third pharyngeal pouch mesenchymal cells critically regulates lymphocyte accumulation in the embryonic thymus.
胸腺提供了一个微环境，可诱导T祖细胞分化为功能性T细胞，并建立一个多样但自身耐受的T细胞库。然而，导致胸腺发育的机制尚未完全了解。我们在此报告了对在包含胸腺原基的第三咽囊表达的基因进行筛选的结果。基于聚合酶链反应（PCR）的cDNA消减筛选，针对在第三咽囊而非第二咽弓的显微切割组织中表达的基因，产生了一种转录因子MafB，其主要在CD45(-)IA(-)PDGFRalpha(+)间充质细胞中表达，甚至在FoxN1缺陷裸鼠的第三咽囊中也可检测到。有趣的是，在MafB缺陷小鼠中，最初在胚胎胸腺中积累的CD45(+)细胞数量显著减少。MafB缺陷小鼠胚胎胸腺中的基因表达改变包括间充质细胞中Wnt3和BMP4以及上皮细胞中CCL21和CCL25的表达降低。这些结果表明，在第三咽囊间充质细胞中表达的MafB对胚胎胸腺中的淋巴细胞积累起着关键调节作用。
