PROJECT SUMMARY (See instructions): The goal of this project is to understand mechanisms of gene regulation in the innate immune response. During the past many years, with support from this grant, we have pioneered work with fundamental implications to our understanding of inflammatory responses. During the past 5 years, the funding stability provided by this MERIT award, enabled us to significantly expand our field of expertise, which resulted in several highly significant and unexpected discoveries, which form the basis of the work proposed over the next 5 years of the award. In particular, we documented a totally novel nucleic acid binding protein CNBP which directs Th1 immune response in vivo and connected lncRNA biology to innate immunity and the inflammatory process. In the proposed extension of this MERIT award we will advance on the foundational observations that linked Cnbp as a specific regulator of IL12p40 gene transcription by defining in detail the molecular mechanisms of Cnbp-dependent control of c-Rel. We will also explore the cell type specific role of Cnbp in controlling Th1 immunity using the T. gondii model. Further, we will explore the contribution of Cnbp in control of the IL23-TH17 response. Lastly, we will expand on our studies of lincRNA-Cox2 to explore regulation of Cox2 and immune responses in vivo.