Xue Hai-Hui, Kovanen Panu E, Pise-Masison Cynthia A, Berg Maria, Radovich Michael F, Brady John N, Leonard Warren J
Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Building 10, Room 7N252, Bethesda, MD 20892-1674, USA.
Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13759-64. doi: 10.1073/pnas.212214999. Epub 2002 Sep 27.
Interleukin (IL)-2 is a type I four-alpha-helical bundle cytokine that plays vital roles in antigen-mediated proliferation of peripheral blood T cells and also is critical for activation-induced cell death. We now demonstrate that IL-2 potently decreases expression of IL-7 receptor alpha chain (IL-7Ralpha) mRNA and protein. The fact that IL-7Ralpha is a component of the receptors for both IL-7 and thymic stromal lymphopoietin (TSLP) suggests that IL-2 can negatively regulate signals by each of these cytokines. Previously it was known that the IL-2 and IL-7 receptors shared the common cytokine receptor gamma chain, gamma(c), which suggested a possible competition between these cytokines for a receptor component. Our findings now suggest a previously unknown type of cross-talk between IL-2 and IL-7 signaling by showing that IL-2 signaling can diminish IL-7Ralpha expression via a phosphatidylinositol 3-kinase/Akt-dependent mechanism.
白细胞介素(IL)-2是一种I型四α螺旋束细胞因子,在外周血T细胞的抗原介导增殖中发挥重要作用,对激活诱导的细胞死亡也至关重要。我们现在证明,IL-2能显著降低IL-7受体α链(IL-7Rα)mRNA和蛋白质的表达。IL-7Rα是IL-7和胸腺基质淋巴细胞生成素(TSLP)受体的组成部分,这一事实表明IL-2可以对这些细胞因子中的每一种信号进行负调控。此前已知IL-2和IL-7受体共享共同的细胞因子受体γ链γ(c),这表明这些细胞因子可能会竞争一个受体成分。我们现在的研究结果表明,IL-2信号传导可通过磷脂酰肌醇3-激酶/蛋白激酶B(Akt)依赖性机制减少IL-7Rα的表达,从而揭示了IL-2和IL-7信号传导之间一种此前未知的相互作用。