摘要：SummaryMany players regulating the CD4+T cell-mediated inflammatory response have already been identified. However, the critical nodes that constitute the regulatory and signaling networks underlying CD4 T cell responses are still missing. Using a correlation-network-guided approach, here we identifiedVIMP(VCP-interacting membrane protein), one of the 25 genes encoding selenoproteins in humans, as a gene regulating the effector functions of human CD4 T cells, especially production of several cytokines including IL2 and CSF2. We identified VIMP as an endogenous inhibitor of cytokine production in CD4 effector T cells via both the E2F5 transcription regulatory pathway and the Ca2+/NFATC2 signaling pathway. Our work not only indicates that VIMP might be a promising therapeutic target for various inflammation-associated diseases but also shows that our network-guided approach can significantly aid in predicting new functions of the genes of interest.Graphical abstractDisplay OmittedHighlights•VIMP is temporally upregulated after TCR stimulation in human CD4 effector T cells•VIMP inhibits cytokine expression in human CD4 effector T cells•VIMP inhibits cytokine expression via the NFATC2/Ca2+signaling pathway•VIMP inhibits cytokine expression by controlling E2F5 expressionImmunology; Cell Biology; Systems Biology
