Molecular mechanisms underlying a distinct specific response mediated by IFNbeta and TNFalpha costimulation.

细胞因子是细胞产生的可溶性介质，用于传递危险信号以激活适当的生物反应。这种反应最终与转录因子的激活有关，转录因子负责一组特定基因的表达。在过去的几十年里，解释特定细胞因子如何触发特定分子途径的分子机制一直是众多研究的焦点。然而，在生理情况下，细胞不太可能一次只受到一种细胞因子的刺激。相反，细胞同时对同一刺激同时产生的“细胞因子鸡尾酒”做出反应。在这种共刺激条件下发生了什么，对于理解细胞因子的功能特别重要，但仍有待阐明。我们的研究以干扰素和肿瘤坏死因子a这两种细胞因子在不同刺激下产生的共刺激作用为原型，揭示了一种新的介导不同基因表达的特异分子途径。我们建议充分描述这一新的机制，这将为我们理解细胞如何在生理情况下对细胞因子做出反应提供新的线索。

Cytokines are soluble mediators produced by cells to transmit signal of danger to activate an appropriate biological response. This response is ultimately linked to the activation of transcription factors that are responsible for the expression of a panel of specific genes. The molecular mechanisms that explain how a specific cytokine triggers a specific molecular pathway have been the focus of numerous studies over the past decades. However, in a physiological situation it is highly unlikely that a cell is stimulated by one cytokine at a time. Instead, a cell simultaneously responds to a "cocktail of cytokines" that are produced simultaneously by the same stimulus. What happens in this condition of costimulation is of particular importance to understand the functions of cytokines, but still remains to be elucidated. Using as a prototype the costimulation by two cytokines named Interferon ß and Tumor Necrosis Factor a both produced in response to various stimuli, our research led us to uncover a novel specific molecular pathway mediating the expression of distinct genes. We propose to fully characterize this novel mechanism that will shed a new light in our understanding of how cells respond to cytokines in a physiological situation.