The Foxn1-dependent transcripts PCOLCE2 and mPPP1R16B are not required for normal thymopoiesis
The Foxn1-dependent transcripts PCOLCE2 and mPPP1R16B are not required for normal thymopoiesis
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DOI：
10.1002/eji.200637474
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发表时间：
2007-09-01
影响因子：
5.4
通讯作者：
Bleul, Conrad C.
中科院分区：
文献类型：
--
作者：
Heinzel, Kornelia;Bleul, Conrad C.
适应性免疫系统依赖于胸腺微环境来产生多样的、自我耐受的T细胞受体库。胸腺微环境的中心细胞组织者是胸腺上皮细胞（TEC）。TEC从内胚层前体细胞的发展是在叉头/翼螺旋转录因子Foxn 1的控制下，但导致这种独特的上皮分化的转录程序尚未在功能上进行研究。在这里，我们表明，表达的前胶原蛋白C-蛋白酶增强子2（PCOLCE 2）是不存在的Foxn 1缺陷TEC。为了研究该基因在TEC分化中的功能作用，我们对PCOLCE 2和编码磷酸酶1调节抑制亚基16 B（mPPP 1 R16 B）的基因进行了遗传失活，后者是Foxn 1缺陷型TEC中缺乏的另一种转录物。缺乏这些转录本之一或两者的小鼠呈现正常的胸腺微环境和不受干扰的胸腺生成。虽然没有证据表明PCOLCE 2和mPPP 1 R16 B在胸腺发育中的功能作用，但我们的研究结果表明，Foxn 1缺陷小鼠的胸腺生成缺乏是由多种功能缺陷引起的。
The adaptive immune system relies on the thymic microenvironment for the production of a diverse, self-tolerant T cell receptor repertoire. The central cellular organizer of the thymic microenvironment is the thymic epithelial cell (TEC). The development of TEC from endodermal precursor cells is under the control of the forkhead/winged helix transcription factor Foxn1 but the transcriptional program that leads to this unique epithelial differentiation has not been investigated functionally. Here, we show that expression of procollagen C-proteinase enhancer 2 (PCOLCE2) is absent in Foxn1-deficient TEC. In order to study the functional role of this gene in TEC differentiation, we have genetically inactivated PCOLCE2 and the gene encoding phosphatase 1 regulatory inhibitory subunit 16B (mPPP1R16B), another transcript lacking in Foxn1-deficient TEC. Mice deficient for either one or both of these transcripts presented a normal thymic microenvironment and undisturbed thymopoiesis. While there is no evidence for a functional role of PCOLCE2 and mPPP1R16B in thymus development, our results suggest that the lack of thymopoiesis in Foxn1-deficient mice is caused by multiple functional defects.