Melichar Heather J, Narayan Kavitha, Der Sandy D, Hiraoka Yoshiki, Gardiol Noemie, Jeannet Gregoire, Held Werner, Chambers Cynthia A, Kang Joonsoo
Department of Pathology, Graduate Program in Immunology and Virology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
Science. 2007 Jan 12;315(5809):230-3. doi: 10.1126/science.1135344.
alphabeta and gammadelta 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 gammadelta-specific gene in the immune system. Using Sox13 transgenic mice, we showed that this transcription factor promotes gammadelta T cell development while opposing alphabeta T cell differentiation. Conversely, mice deficient in Sox13 expression exhibited impaired development of gammadelta T cells but not alphabeta 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.
αβ和γδ T细胞起源于胸腺中的一个共同的多能前体细胞群体，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γδ特异性基因。利用Sox13转基因小鼠，我们发现该转录因子促进γδ T细胞发育，同时抑制αβ T细胞分化。相反，Sox13表达缺陷的小鼠γδ T细胞发育受损，但αβ T细胞发育未受影响。SOX13发挥功能的一种机制是抑制发育过程中重要的Wnt/T细胞因子（TCF）信号通路。因此，我们的数据揭示了一条主导途径，该途径调节这两种T淋巴细胞谱系的发育命运。
