%0 Journal Article %T CD4 + T cells require Ikaros to inhibit their differentiation towards a pathogenic cell fate %+ Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC) %+ IGBMC, GenomEast Platform, 1 Rue Laurent Fries,BP 10142, F-67404 Illkirch Graffenstaden, France %+ University of Freiburg [Freiburg] %+ Centre for Biological Signaling Studies [Freiburg] (BIOSS) %A Bernardi, Chiara %A Maurer, Gaëtan %A Ye, Tao %A Marchal, Patricia %A Jost, Bernard %A Wissler, Manuela %A Maurer, Ulrich %A Kastner, Philippe %A Chan, Susan %A Charvet, Céline %< avec comité de lecture %@ 0027-8424 %J Proceedings of the National Academy of Sciences of the United States of America %I National Academy of Sciences %V 118 %N 17 %P e2023172118 %8 2021-04-23 %D 2021 %R 10.1073/pnas.2023172118 %K GM-CSF %K IL-17 %K Ikaros %K pathogenicity %K proinflammatory cytokines %Z Life Sciences [q-bio]Journal articles %X The production of proinflammatory cytokines, particularly granulocyte-macrophage colony-stimulating factor (GM-CSF), by pathogenic CD4+ T cells is central for mediating tissue injury in inflammatory and autoimmune diseases. However, the factors regulating the T cell pathogenic gene expression program remain unclear. Here, we investigated how the Ikaros transcription factor regulates the global gene expression and chromatin accessibility changes in murine T cells during Th17 polarization and after activation via the T cell receptor (TCR) and CD28. We found that, in both conditions, Ikaros represses the expression of genes from the pathogenic signature, particularly Csf2, which encodes GM-CSF. We show that, in TCR/CD28-activated T cells, Ikaros binds a critical enhancer downstream of Csf2 and is required to regulate chromatin accessibility at multiple regions across this locus. Genome-wide Ikaros binding is associated with more compact chromatin, notably at multiple sites containing NFκB or STAT5 target motifs, and STAT5 or NFκB inhibition prevents GM-CSF production in Ikaros-deficient cells. Importantly, Ikaros also limits GM-CSF production in TCR/CD28-activated human T cells. Our data therefore highlight a critical conserved transcriptional mechanism that antagonizes GM-CSF expression in T cells. %G English %2 https://cnrs.hal.science/hal-03362243/document %2 https://cnrs.hal.science/hal-03362243/file/Bernardi%20et%20al%20main%20manuscript%20and%20information.pdf %L hal-03362243 %U https://cnrs.hal.science/hal-03362243 %~ INSERM %~ CNRS %~ IGBMC %~ UNIV-STRASBG %~ SITE-ALSACE