The development of an innovative therapy for autoimmune diseases by controlling FOXP3, a unique transcription factors of the regulatory T cells

CD4（+）CD25（+）调节性T细胞（Treg）通过控制免疫应答来促进免疫系统的稳态。越来越多的研究表明，调节性T细胞数量或功能的调控将为自身免疫性疾病的治疗带来新的突破。最近，FOXP3被鉴定为Treg的独特转录因子。为了了解FOXP3的功能机制，我们进行了两次酵母杂交筛选，发现SOCS1和SOCS3是FOXP3的配偶体候选者。在本研究中，我们发现内源性SOCS3与FLAG标记的FOXP3在FOXP3转染的Treg细胞克隆中免疫共沉淀，表明SOCS3与FOXP3相关。然而，通过逆转录病毒载体表达的shRNA对SOCS1或SOCS3进行RNA沉默并没有揭示Treg的抑制活性的明显改变。虽然我们的结果可能是由于与通过靶向降低SOCS表达相比，FOXP3的表达相对较高，但SOCS 3可能对FOXP3的调节活性没有贡献。相反，如已知的，Treg发育在SOCS1缺陷小鼠中受到干扰，并且SOCS家族通过泛素连接酶活性参与蛋白质降解，SOCS3可能在胸腺中T细胞的发育或效应T细胞中Foxp3的降解中发挥一定作用。

CD4(+) CD25(+) regulatory T cells (Treg) contributes in homeostasis of the immune system by controlling an immune response. Accumulating studies indicate that the control in the number or function of Treg lead to innovation in the treatment of autoimmune diseases. Recently, FOXP3 was identified to be a unique transcription factor for Treg. In order to understand the functional mechanism of FOXP3, we conducted two yeast hybrid screening, and found that SOCS1 and 3 are the partner candidates of FOXP3. In this study we found that endogenous SOCS3 was co-immunoprecipitated with FLAG-tagged FOXP3 in FOXP3-transfected Treg cell clone, indicating that SOCS3 is associated with FOXP3. However, RNA silencing of either SOCS1 or SOCS3 by shRNA expressed by retroviral vector did not reveal a distinct alternation in the suppressive activity of Treg. Although our result would be due to the relatively higher expression of FOXP3 in comparison with the decrease of SOCS expression by targeting, SOCS3 might not contribute in the regulatory activity of FOXP3. Rather, as is known that Treg development is disturbed in SOCS1-deficient mice and that SOCS family contribute in the protein degradation via ubiquitin-ligase activity, SOCS3 might play some role in the development of T cells in the thymus or degradation of Foxp3 in effector T cells.