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

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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.