Identification of VIMP/SELS as a gene inhibiting cytokine production in human CD4+ effector T cells

Many 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 identified VIMP (VCP-interacting membrane protein, also known as SELS), 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. We performed transcriptomic analysis in human primary CD4 Teffs (CD4+CD25- cells). The Teffs were transfected with specific siRNA against VIMP/SELS or the scrambled control siRNA (si_NS) for 1 day followed by 1 day stimulation using Dynabeads Human T-activator CD3/CD28 for T cell expansion and activation (11131D, ThermoFischer Scientific) (for details, see the section 'Protocols'). The Affymetrix human Gene 2.0 ST Arrays were used and analyzed at EMBL Genomics core facilities (Heidelberg. Germany). Array data was processed by Affymetrix Expression Console v1.4 using Exon-level analysis. No technical replicates were performed. But the results were obtained from 3 different healthy donors.