Nakajima H, Liu X W, Wynshaw-Boris A, Rosenthal L A, Imada K, Finbloom D S, Hennighausen L, Leonard W J
Laboratory of Molecular Immunology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Immunity. 1997 Nov;7(5):691-701. doi: 10.1016/s1074-7613(00)80389-1.
Stat5a was identified as a prolactin-induced transcription factor but also is activated by other cytokines, including interleukin-2 (IL-2) and IL-7. We have now analyzed the immune system of Stat5a-deficient mice. Stat5a-/- splenocytes exhibited defective IL-2-induced expression of the IL-2 receptor alpha chain (IL-2R alpha), a protein that together with IL-2R beta and the common cytokine receptor gamma chain (gamma(c)) mediates high-affinity IL-2 binding. Correspondingly, Stat5a-/- splenocytes exhibited markedly decreased proliferation to IL-2, although maximal proliferation was still achieved at IL-2 concentrations high enough to titrate intermediate-affinity IL-2R beta/gamma(c) receptors. Thus, defective Stat5a expression results in diminished proliferation by an indirect mechanism, resulting from defective receptor expression. Correspondingly, we show that Stat5a is essential for maximal responsiveness to antigenic stimuli in vivo, underscoring the physiological importance of IL-2-induced IL-2R alpha expression.
Stat5a被鉴定为一种催乳素诱导的转录因子，但也可被包括白细胞介素-2（IL-2）和IL-7在内的其他细胞因子激活。我们现在分析了Stat5a缺陷小鼠的免疫系统。Stat5a基因敲除的脾细胞表现出IL-2诱导的IL-2受体α链（IL-2Rα）表达缺陷，IL-2Rα蛋白与IL-2Rβ和共同细胞因子受体γ链（γ(c)）一起介导高亲和力的IL-2结合。相应地，Stat5a基因敲除的脾细胞对IL-2的增殖明显减少，尽管在足以滴定中等亲和力IL-2Rβ/γ(c)受体的高IL-2浓度下仍能实现最大增殖。因此，Stat5a表达缺陷通过受体表达缺陷的间接机制导致增殖减少。相应地，我们表明Stat5a对于体内对抗抗原刺激的最大反应性至关重要，这突出了IL-2诱导的IL-2Rα表达的生理重要性。
