Identification of VIMP as a gene inhibiting cytokine production in human CD4+ effector T cells by Capelle et al.
Using a systems-immunology correlation-network-guided approach, here we identified VIMP (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.
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Figure 4C with western blotting results. The samples from left to right follow the order below (after excluding the lanes with ladders): 1, si_NS 0h, 2, si_NS 1h, 3, si_NS 4h, 4, si_NS 24h, 5, si_VIMP 0h, 6, si_VIMP 1h, 7, si_VIMP 4h, 8, si_VIMP 24h, si_NS, the Teff cells were first treated with control non-specific siRNA for 1 day; si_VIMP, the Teff cells were first treated with VIMP-specific siRNA for 1 day. Those cells were then stimulated with anti-CD3/-CD28 ab for different indicated periods (h). For more details, please refer to Figure 4C of the manuscript and the Transparent Methods. Of note, the ladders might be loaded in different positions for the gels detecting different targeted proteins. For the gel that detects pNFATC2, only the top line of lanes presented the samples of interests for Figure 4C of the concerned work (Capelle et al., 2021, iScience, https://doi.org/10.1016/j.isci.2021.102289 or https://www.cell.com/iscience/fulltext/S2589-0042(21)00257-1).