尽管Foxp3缺失，但抑制功能得以保留：对调节性T细胞身份的深入了解。 - Suppr | 超能文献

Abstract

Regulatory T (Treg) cells are essential for maintaining immune homeostasis, with Foxp3 acting as the master transcription factor governing their differentiation and function. The acquisition of effector signatures in Treg cells is closely tied to the surrounding tissue-specific immune environment and typically occurs alongside Foxp3 expression. In this study, we investigated the transcriptomic and functional consequences of Treg-mediated regulation in a Th2-driven disease setting. The application of both systems and disease models allowed us to mimic Th2-mediated environments. We could demonstrate Th2-driven loss of Foxp3 expression in Treg cells and . Transcriptomic analysis revealed a maintained Treg signature despite the loss of active Foxp3 expression. Functional characterization of Tregs both and uncovered a preserved suppressive capacity even in the absence of Foxp3. Our findings unveil that, despite loss of Foxp3, a preserved Treg signature remains intact enabling the regulation of Th2-mediated diseases. The persistence of this regulatory transcriptome highlights the importance for developing Treg-cell therapy strategies in cancer and autoimmune diseases independent of Foxp3 expression.

摘要

调节性T（Treg）细胞对于维持免疫稳态至关重要，其中Foxp3作为主导转录因子，调控其分化和功能。Treg细胞中效应子特征的获得与周围组织特异性免疫环境密切相关，通常与Foxp3表达同时发生。在本研究中，我们调查了在Th2驱动的疾病环境中Treg介导的调节作用的转录组学和功能后果。应用系统和疾病模型使我们能够模拟Th2介导的环境。我们能够证明在Treg细胞中Th2驱动的Foxp3表达缺失。转录组分析显示，尽管活性Foxp3表达缺失，但Treg特征得以维持。对Treg细胞的功能表征揭示，即使在没有Foxp3的情况下，其抑制能力仍得以保留。我们的研究结果表明，尽管Foxp3缺失，但保留的Treg特征仍然完整，能够调节Th2介导的疾病。这种调节性转录组的持续存在凸显了在癌症和自身免疫性疾病中开发独立于Foxp3表达的Treg细胞治疗策略的重要性。