Synergy between IL-6 and TGF-β signaling promotes FOXP3 degradation

[摘要] The forkhead family transcription factor FOXP3 is critical for the differentiation and function of CD4⁺ CD25⁺ regulatory T cells (Treg). How FOXP3 protein level is negatively regulated under the inflammatory microenvironment is largely unknown. Here we report that the combination of transforming growth factor-beta (TGF-β) and IL-6 treatment (IL-6/TGF-β) can synergistically downregulate FOXP3 at the posttranslational level by promoting FOXP3 protein degradation. In our FOXP3 overexpression model, we found that IL-6/TGF-β treatment upregulated IL-6R expression but did not affect the stability of FOXP3 mRNA. Moreover, we found that the proteasome inhibitor MG132 could inhibit IL-6/TGF-β-mediated downregulation of FOXP3 protein, which reveals a potential pathway for modulating Treg activity by preventing FOXP3 degradation during inflammation.

[学科分类] 生理学与病理学

[关键词] FOXP3;Treg;instability;IL-6;TGF-β;proteasome