Identification of VIMP as a gene inhibiting cytokine production in human CD4+ effector T cells
Christophe M. Capelle,
Ni Zeng,
Egle Danileviciute,
Sabrina Freitas Rodrigues,
Markus Ollert,
Rudi Balling,
Feng Q. He
Affiliations
Christophe M. Capelle
Department of Infection and Immunity, Luxembourg Institute of Health (LIH), 29, rue Henri Koch, 4354 Esch-sur-Alzette, Luxembourg; Faculty of Science, Technology and Medicine, University of Luxembourg, 2, avenue de Université, 4365 Esch-sur-Alzette, Luxembourg
Ni Zeng
Department of Infection and Immunity, Luxembourg Institute of Health (LIH), 29, rue Henri Koch, 4354 Esch-sur-Alzette, Luxembourg
Egle Danileviciute
Department of Infection and Immunity, Luxembourg Institute of Health (LIH), 29, rue Henri Koch, 4354 Esch-sur-Alzette, Luxembourg; Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 6, avenue du Swing, 4367 Belvaux, Luxembourg
Sabrina Freitas Rodrigues
Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 6, avenue du Swing, 4367 Belvaux, Luxembourg
Markus Ollert
Department of Infection and Immunity, Luxembourg Institute of Health (LIH), 29, rue Henri Koch, 4354 Esch-sur-Alzette, Luxembourg; Department of Dermatology and Allergy Center, Odense Research Center for Anaphylaxis (ORCA), University of Southern Denmark, Odense, 5000 C, Denmark
Rudi Balling
Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 6, avenue du Swing, 4367 Belvaux, Luxembourg
Feng Q. He
Department of Infection and Immunity, Luxembourg Institute of Health (LIH), 29, rue Henri Koch, 4354 Esch-sur-Alzette, Luxembourg; Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, 6, avenue du Swing, 4367 Belvaux, Luxembourg; Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany; Corresponding author
Summary: 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), 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.
