通过转录因子SOX13调节 gamma delta 与 alphabet T 淋巴细胞的分化
Heather J Melichar1, Kavitha Narayan, Sandy D Der
1Department of Pathology, Graduate Program in Immunology and Virology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
Science (New York, N.Y.)
|January 16, 2007
概括
Sox13是指导T细胞发育的关键转录因子. 它促进了 gamma-delta T 细胞的发育,同时抑制了 alpha-beta T 细胞的分化,揭示了淋巴细胞谱系的决定中占主导地位的途径.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 发育生物学 发展生物学
背景情况:
- 对于适应性免疫来说至关重要的T淋巴细胞分化为两种主要类型:alphabeta和gammadelta T细胞.
- 这些T细胞系起源于胸腺中的一个共同的前体,但它们分化的分子调节者仍然在很大程度上是未知的.
研究的目的:
- 确定控制alphabeta和gammadeltaT细胞之间的血统命运决定的分子机制.
- 研究转录因子Sox13在T细胞发育中的作用.
主要方法:
- 利用Sox13转基因小鼠研究其在T细胞发育中的功能.
- 产生和分析Sox13缺乏的小鼠,以评估其对T细胞谱系承诺的必要性.
- 研究了Sox13对Wnt/T细胞因子 (TCF) 信号通路的影响.
主要成果:
- 鉴定出Sox13是一种高分子三角形T细胞特异性基因.
- 过度表达Sox13促进了马氏体T细胞的发育,并抑制了alphabeta T细胞的分化.
- 索克斯13缺乏导致Gamma Delta T细胞发育受损,而不会影响alphabeta T细胞发育.
- Sox13 抑制了通过 Wnt/TCF 途径传输信号.
结论:
- 索克斯13作为一个关键调节剂,促进马氏体T细胞谱系和抑制alphabeta T细胞谱系.
- Wnt/TCF路径是一个关键的目标,通过该路径,Sox13可以发挥其确定血统的功能.
- 这些发现阐明了控制T淋巴细胞发育命运的主导分子途径.
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