Cytokines belonging to the common gamma chain (γ_c) family depend on the shared γ_c receptor subunit for signaling. We report the existence of a fast, cytokine-induced pathway cross-talk acting at the receptor level, resulting from a limiting amount of γ_c on the surface of T cells. We found that this limited abundance of γ_c reduced interleukin-4 (IL-4) and IL-21 responses after IL-7 preexposure but not vice versa. Computational modeling combined with quantitative experimental assays indicated that the asymmetric cross-talk resulted from the ability of the “private” IL-7 receptor subunits (IL-7Rα) to bind to many of the γ_c molecules even before stimulation with cytokine. Upon exposure of T cells to IL-7, the high affinity of the IL-7Rα:IL-7 complex for γ_c further reduced the amount of free γ_c in a manner dependent on the concentration of IL-7. Measurements of bioluminescence resonance energy transfer (BRET) between IL-4Rα and γ_c were reduced when IL-7Rα was overexpressed. Furthermore, in a system expressing IL-7Rα, IL-4Rα, and γ_c, BRET between IL-4Rα and γ_c increased after IL-4 binding and decreased when cells were preexposed to IL-7, supporting the assumption that IL-7Rα and the IL-7Rα:IL-7 complex limit the accessibility of γ_c for other cytokine receptor complexes. We propose that in complex inflammatory environments, such asymmetric cross-talk establishes a hierarchy of cytokine responsiveness.

属于共同的γ链（γ细胞因子_Ç）家族依赖于共享γ _Ç受体亚基用于信令。我们报告了一种快速，细胞因子诱导的途径在受体水平作用串扰的存在，从γ限制量所得_Ç T细胞的表面上。我们发现，这种有限的γ丰度_Ç白介素-4（IL-4）和IL-21的响应后IL-7预曝光而不是相反减小。计算建模与定量实验分析相结合表明，非对称的串扰导致从“私人” IL-7受体亚基（IL-7Rα）结合的能力，许多的γ _Ç分子，甚至在用细胞因子刺激之前。对T细胞暴露于IL-7，IL-7Rα的高亲和力：IL-7复合物γ _Ç进一步减少游离γ量_Ç在依赖于IL-7的浓度的方式。IL-4Rα和γ之间的生物发光共振能量转移（BRET）的测量_Ç当IL-7Rα过表达减少。此外，在表达IL-7Rα，IL-4Rα和系统γ _Ç，IL-4Rα和γ之间BRET _Ç后IL-4结合增加，并且当细胞被预曝光到IL-7下降，支撑假设IL-7Rα和IL-7Rα：IL-7复杂极限γ的可接近_ç用于其他细胞因子受体复合物。我们建议在复杂的炎症环境中，这种不对称的串扰建立了细胞因子反应性的层次结构。