Rattazzi Lorenza, Piras Giuseppa, Brod Samuel, Smith Koval, Ono Masahiro, D'Acquisto Fulvio
William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London , London , UK.
Department of Life Science, Faculty of Natural Science, Imperial College of Science, Technology and Medicine , London , UK.
Front Immunol. 2016 Sep 30;7:381. doi: 10.3389/fimmu.2016.00381. eCollection 2016.
T cells are known to be plastic and to change their phenotype according to the cellular and biochemical milieu they are embedded in. In this study, we transposed this concept at a macroscopic level assessing whether changes in the environmental housing conditions of C57/BL6 mice would influence the phenotype and function of T cells. Our study shows that exposure to 2 weeks in an enriched environment (EE) does not impact the T cell repertoire and causes no changes in the early TCR-driven activation events of these cells. Surprisingly, however, T cells from enriched mice showed a unique T helper effector cell phenotype upon differentiation . This was featured by a significant reduction in their ability to produce IFN-γ and by an increased release of IL-10 and IL-17. Microarray analysis of these cells also revealed a unique gene fingerprint with key signaling pathways involved in autoimmunity being modulated. Together, our results provide first evidence for a specific effect of EE on T cell differentiation and its associated changes in gene expression profile. In addition, our study sheds new light on the possible mechanisms by which changes in environmental factors can significantly influence the immune response of the host and favor the resolution of the inflammatory response.
已知T细胞具有可塑性,会根据其所处的细胞和生化环境改变其表型。在本研究中,我们将这一概念应用于宏观层面,评估C57/BL6小鼠环境饲养条件的变化是否会影响T细胞的表型和功能。我们的研究表明,在丰富环境(EE)中暴露2周不会影响T细胞库,也不会导致这些细胞早期TCR驱动的激活事件发生变化。然而,令人惊讶的是,来自丰富环境小鼠的T细胞在分化时表现出独特的辅助性T效应细胞表型。其特征是产生IFN-γ的能力显著降低,以及IL-10和IL-17的释放增加。对这些细胞的微阵列分析还揭示了一个独特的基因指纹,其中涉及自身免疫的关键信号通路受到了调节。总之,我们的结果首次证明了EE对T细胞分化及其相关基因表达谱变化具有特定影响。此外,我们的研究为环境因素变化可显著影响宿主免疫反应并促进炎症反应消退的可能机制提供了新的线索。