Balciunaite Gina, Keller Marcel P, Balciunaite Egle, Piali Luca, Zuklys Saulius, Mathieu Yves D, Gill Jason, Boyd Richard, Sussman Daniel J, Holländer Georg A
Pediatric Immunology, Department of Research and Clinical-biological Sciences, and the Children's Hospital, University of Basel, Basel, Switzerland.
Nat Immunol. 2002 Nov;3(11):1102-8. doi: 10.1038/ni850. Epub 2002 Oct 15.
T cell development and selection require the fully mature and diverse epithelial microenvironment of the thymus. Acquisition of these characteristics is dependent on expression of the forkhead (also known as winged-helix) transcription factor FoxN1, as a lack of functional FoxN1 results in aberrant epithelial morphogenesis and an inability to attract lymphoid precursors to the thymus primordium. However, the transcriptional control of Foxn1 expression has not been elucidated. Here we report that secreted Wnt glycoproteins, expressed by thymic epithelial cells and thymocytes, regulate epithelial Foxn1 expression in both autocrine and paracrine fashions. Wnt molecules therefore provide regulatory signals critical for thymic function.
T细胞的发育和选择需要胸腺中完全成熟且多样的上皮微环境。这些特征的获得依赖于叉头（也称为翼状螺旋）转录因子FoxN1的表达，因为缺乏功能性FoxN1会导致上皮形态发生异常，并且无法将淋巴样前体细胞吸引到胸腺原基。然而，Foxn1表达的转录调控尚未阐明。在此，我们报告由胸腺上皮细胞和胸腺细胞表达的分泌型Wnt糖蛋白以自分泌和旁分泌方式调节上皮细胞中Foxn1的表达。因此，Wnt分子提供了对胸腺功能至关重要的调节信号。
