The innate immune response to pathogens involves the expression and secretion of inflammatory cytokines that act to facilitate eradication of the infecting pathogen. The dysregulation of cytokine production (chronic inflammation) can have negative effects on the host. Therefore, a fundamental understanding of the molecular mechanisms regulating inflammation is essential for the development of therapeutic approaches for inflammatory disorders. We identify a novel role for the transcription factor GLI3 in regulating cytokine expression in response to TLR-TRIF signaling. GLI3 KO in monocytes induces a phenotype that indicates GLI3 associates with inflammatory pathways in response to TLR-TRIF stimulation. In this proposal, we will further elucidate the role of GLI3 in regulating cytokine expression in monocytes and explore the relevance of this regulation in inflammatory responses.