TY - JOUR
T1 - Identification of VIMP as a gene inhibiting cytokine production in human CD4+ effector T cells
AU - Capelle, Christophe M.
AU - Zeng, Ni
AU - Danileviciute, Egle
AU - Rodrigues, Sabrina Freitas
AU - Ollert, Markus
AU - Balling, Rudi
AU - He, Feng Q.
N1 - Funding Information:
We thank Annegrät Daujeumont, Alexandre Baron, and Olga Kondratyeva for their expert technical support. We particularly appreciate Luxembourg Red Cross for providing buffy coats to us. The Feng He group was supported by Luxembourg National Research Fund ( FNR ) through different programs including PRIDE ( CRITICS DTU) /10907093 to support C.M.C.; individual Aide à la Formation Recherche (AFR) grants PHD-2014-1/7603621 and PHD-2015-1/9989160 to support E.D. and N.Z. respectively; and intramural funding within Luxembourg Institute of Health and Luxembourg Center for Systems Biomedicine from Ministère de l'Enseignement supérieur et de la Recherche (MESR). M.O. was supported as coordinator by FNR through the FNR PRIDE program for a doctoral training unit (DTU, PRIDE/NEXTIMMUNE/11012546 ). Some icons in the graphical abstract were created with BioRender.com .
Publisher Copyright:
© 2021 The Author(s)
PY - 2021/4/23
Y1 - 2021/4/23
N2 - 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.
AB - 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.
KW - Cell Biology
KW - Immunology
KW - Systems Biology
UR - http://www.scopus.com/inward/record.url?scp=85103336051&partnerID=8YFLogxK
UR - https://www.ncbi.nlm.nih.gov/pubmed/33851102
U2 - 10.1016/j.isci.2021.102289
DO - 10.1016/j.isci.2021.102289
M3 - Article
C2 - 33851102
AN - SCOPUS:85103336051
SN - 2589-0042
VL - 24
SP - 102289
JO - iScience
JF - iScience
IS - 4
M1 - 102289
ER -