Regulation of γδ versus αβ T lymphocyte differentiation by the transcription factor SOX13
Regulation of γδ versus αβ T lymphocyte differentiation by the transcription factor SOX13
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DOI：
10.1126/science.1135344
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发表时间：
2007-01-12
期刊：
影响因子：
56.9
通讯作者：
Kang, Joonsoo
中科院分区：
文献类型：
--
作者：
Melichar, Heather J.;Narayan, Kavitha;Kang, Joonsoo
αβ和γδT细胞起源于胸腺中常见的、多潜能的前体细胞群，但调节这种谱系命运决定的分子机制尚不清楚。我们已将 Sox13 鉴定为免疫系统中的 γ δ 特异性基因。使用 Sox13 转基因小鼠，我们发现该转录因子促进 gd T 细胞发育，同时对抗 ab T 细胞分化。相反，Sox13 表达缺陷的小鼠表现出 gd T 细胞发育受损，但 ab T 细胞则没有。 SOX13 功能的机制之一是抑制发育重要的 Wnt/T 细胞因子 (TCF) 途径的信号传导。因此，我们的数据揭示了调节这两个 T 淋巴细胞谱系发育命运的主导途径。
alpha beta and gamma delta T cells originate from a common, multipotential precursor population in the thymus, but the molecular mechanisms regulating this lineage-fate decision are unknown. We have identified Sox13 as a gamma delta-specific gene in the immune system. Using Sox13 transgenic mice, we showed that this transcription factor promotes gd T cell development while opposing ab T cell differentiation. Conversely, mice deficient in Sox13 expression exhibited impaired development of gd T cells but not ab T cells. One mechanism of SOX13 function is the inhibition of signaling by the developmentally important Wnt/T cell factor (TCF) pathway. Our data thus reveal a dominant pathway regulating the developmental fate of these two lineages of T lymphocytes.