SOCS3 is a crucial feedback inhibitor of several cytokine pathways with potential regulatory functions during T cell receptor activation. A role of SOCS3 in IL-7-dependent homeostatic mechanisms has been assumed but the underlying mechanisms remain unclear. We investigated the role of SOCS3 in IL-7 receptor α-chain (IL-7Rα) expression and IL-7 effects on activated human CD4+ T cells. SOCS3 expression modulation by lentiviral transduction combined with T cell phenotyping, receptor signalling analysis, and a novel competitive in vitro assay were applied. Time course analyses following T-cell activation showed IL-7Rα re-expression after initial down-regulation that was accompanied by increased SOCS3 expression starting on day 2. T cells with low SOCS3 expression (SOCS3kd ) had decreased IL-7Rα levels due to impaired re-expression. SOCS3 mediated effects on IL-7Rα were not affected by recombinant IL-7 or blocking of IL-2. We found no evidence for SOCS3 effects on IL7RA transcriptional regulation. Functionally, SOCS3kd T cells showed decreased IL-7-dependent proliferation as compared to vector control T cells under competitive in vitro conditions. This impaired IL-7 response of SOCS3kd T cells was accompanied by decreased STAT5 phosphorylation late during IL-7 signalling. We identified a novel SOCS3 function in IL-7Rα regulation during T-cell activation with crucial implications for IL-7-dependent mechanisms.

中文翻译：

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细胞因子信号传导抑制剂3对于T细胞活化和白介素7依赖性增殖后白介素7受体的重新表达至关重要。

SOCS3是几种细胞因子途径的关键反馈抑制剂，在T细胞受体激活过程中具有潜在的调节功能。已经假定SOCS3在依赖IL-7的稳态机制中的作用，但其潜在机制仍不清楚。我们调查了SOCS3在IL-7受体α链（IL-7Rα）表达中的作用以及IL-7对活化的人CD4 + T细胞的影响。慢病毒转导结合T细胞表型，受体信号分析和新型竞争性体外测定应用SOCS3表达调节。T细胞活化后的时程分析显示，初始下调后IL-7Rα重新表达，并伴随着从第2天开始的SOCS3表达增加。具有低SOCS3表达的T细胞（SOCS3kd）由于受损而降低了IL-7Rα水平。重新表达。SOCS3介导的对IL-7Rα的作用不受重组IL-7或IL-2阻滞的影响。我们没有发现SOCS3对IL7RA转录调控的影响的证据。在功能上，与竞争性体外条件下的载体对照T细胞相比，SOCS3kd T细胞显示出降低的IL-7依赖性增殖。SOCS3kd T细胞的IL-7反应受损，伴随IL-7信号传导后期STAT5磷酸化水平降低。我们在T细胞活化过程中发现了IL-7Rα调控中的新型SOCS3功能，对IL-7依赖性机制具有至关重要的意义。与竞争性体外条件下的载体对照T细胞相比，SOCS3kd T细胞显示出降低的IL-7依赖性增殖。SOCS3kd T细胞的IL-7反应受损，伴随IL-7信号传导后期STAT5磷酸化水平降低。我们在T细胞活化过程中发现了IL-7Rα调控中的新型SOCS3功能，对IL-7依赖性机制具有至关重要的意义。与竞争性体外条件下的载体对照T细胞相比，SOCS3kd T细胞显示出降低的IL-7依赖性增殖。SOCS3kd T细胞的IL-7反应受损，伴随IL-7信号传导后期STAT5磷酸化水平降低。我们在T细胞活化过程中发现了IL-7Rα调控中的新型SOCS3功能，对IL-7依赖性机制具有至关重要的意义。