Cytokines play fundamental roles in the regulation of immune responses against pathogens and were shown to be crucial in several pathological conditions such as autoimmune diseases, immune deficiencies and cancer. Cytokine production is highly regulated and activation of cytokine gene transcription is a key step in inflammatory processes. In fact, cytokine mis-regulation can lead to immune deficiencies, cancer and autoimmune diseases making them appealing therapeutic targets. Even though cytokine regulation has been well studied, little is known about which transcription factors (TFs) bind to their regulatory regions and how they control cytokine expression. To be able to fully comprehend cytokine transcriptional regulation we need to undertake a systems biology approaches that will provide an integrated view of how cytokines are orchestrated during an immune response. Our research aim is to delineate a human cytokine regulatory network. We are identifying the TFs that can bind the promoters and other known regulatory regions for all human cytokines taking advantage of a new enhanced yeast one hybrid assay pipeline recently developed in the Walhout laboratory. We will model the protein-DNA interactions into a gene regulatory network (GRN) depicting the cytokine genes, the TFs and their relationships, and will integrate this GRN with publicly available expression data. Finally, our aim is to determine the regulatory consequences of the physical interactions identified. Our hope is to expand the current knowledge of cytokine regulation which may provide leads to identify new therapeutic targets for multiple immune related diseases.