Allergic asthma that is caused by inhalation of house dust mites (HDMs) is mainly mediated by Th2 cells. Recently, the roles of Sox (SRY-related high-mobility-group (HMG)-box) family members in various immune responses have been investigated. However, the roles of Sox12, a member of the SoxC group, in Th2 cell differentiation and allergic airway inflammation, remain unknown. We showed that Sox12 mRNA was significantly increased during Th2 cell differentiation. In vivo, HDM-induced eosinophil infiltration into the lung and Th2 cell differentiation were exacerbated in Sox12^−/− mice compared with those in control Sox12^+/− mice. In vitro, Sox12^−/− CD4⁺ T cells that were cultured under Th2 conditions had increased production of Th2 cytokines and GATA3 protein compared with those of control Sox12^+/− CD4⁺ T cells. Importantly, forced expression of Sox12 decreased the protein levels of GATA3 in CD4⁺ T cells under Th2 conditions without affecting mRNA expression. Furthermore, Sox12 induced degradation of GATA3 through the proteasome pathway in CD4⁺ T cells. Consistently, Sox12 enhanced ubiquitination of GATA3, which was mediated by the E3 ligase Fbw7. Finally, we found that Fbw7 knockdown partly abrogated Sox12-mediated GATA3 suppression in CD4⁺ T cells. Taken together, these results suggest that Sox12 suppresses Th2 cell differentiation by accelerating Fbw7-mediated GATA3 degradation, and attenuates HDM-induced allergic inflammation.

因吸入屋尘螨 (HDM) 引起的过敏性哮喘主要由 Th2 细胞介导。最近，人们对 Sox（SRY 相关高迁移率基团 (HMG)-box）家族成员在各种免疫反应中的作用进行了研究。然而，Sox12（SoxC 组的成员）在 Th2 细胞分化和过敏性气道炎症中的作用仍不清楚。我们发现 Sox12 mRNA 在 Th2 细胞分化过程中显着增加。在体内，与对照 Sox12 ^+/-小鼠相比，HDM 诱导的嗜酸性粒细胞浸润肺部和 Th2 细胞分化在 Sox12 ^−/−小鼠中加剧。在体外，与对照Sox12 ^+/- CD4 ⁺ T细胞相比，在Th2条件下培养的Sox12 ^-/- CD4 ⁺ T细胞增加了Th2细胞因子和GATA3蛋白的产生。重要的是，Sox12的强制表达降低了Th2条件下CD4 ⁺ T细胞中GATA3的蛋白水平，而不影响mRNA表达。此外，Sox12 通过 CD4 ⁺ T 细胞中的蛋白酶体途径诱导 GATA3 降解。一致地，Sox12 增强了 GATA3 的泛素化，这是由 E3 连接酶 Fbw7 介导的。最后，我们发现 Fbw7 敲低部分消除了 CD4 ⁺ T 细胞中 Sox12 介导的 GATA3 抑制。综上所述，这些结果表明 Sox12 通过加速 Fbw7 介导的 GATA3 降解来抑制 Th2 细胞分化，并减轻 HDM 诱导的过敏性炎症。