Ye S K, Maki K, Kitamura T, Sunaga S, Akashi K, Domen J, Weissman I L, Honjo T, Ikuta K
Department of Medical Chemistry, Faculty of Medicine, Kyoto University, Japan.
Immunity. 1999 Aug;11(2):213-23. doi: 10.1016/s1074-7613(00)80096-5.
IL-7 receptor (IL-7R) plays critical roles in lymphocyte development by promoting survival and proliferation and by inducing V(D)J recombination in TCR and Ig loci. Here, we demonstrate that IL-7R-activated Stat5 binds to consensus motifs in the 5' regions of Jgamma segments and induces germline transcripts. We also show that a constitutively active form of Stat5 restores V-J recombination of TCRgamma genes and partially rescues T cell development from IL-7R(-/-) T cell precursors, especially in favor of gammadelta T cells. Therefore, this study reveals a potential role of Stat5 in T cell development and also implies that IL-7R may control the accessibility of the TCRgamma locus through Stat5-induced germline transcription.
白细胞介素7受体(IL-7R)通过促进存活和增殖以及在T细胞受体(TCR)和免疫球蛋白(Ig)基因座中诱导V(D)J重组,在淋巴细胞发育中发挥关键作用。在此,我们证明IL-7R激活的Stat5与Jγ片段5'区域中的共有基序结合并诱导种系转录本。我们还表明,Stat5的组成型活性形式可恢复TCRγ基因的V-J重组,并部分挽救IL-7R(-/-)T细胞前体的T细胞发育,尤其有利于γδT细胞。因此,本研究揭示了Stat5在T细胞发育中的潜在作用,也暗示IL-7R可能通过Stat5诱导的种系转录来控制TCRγ基因座的可及性。