CD4+T cells require Ikaros to inhibit their differentiation toward a pathogenic cell fate

Significance The production of proinflammatory cytokines, particularly granulocyte-macrophage colony-stimulating factor, by CD4 + T cells is a key process for amplifying immune responses but can also lead to harmful tissue damage in pathologies like multiple sclerosis and Covid-19. Correctly controlling the expression of proinflammatory cytokines is therefore of major interest. However, the pathogenic signature of CD4 + T cells relies on a transcriptional program that is thus far poorly understood. Here, we identified the transcription factor Ikaros as an essential transcriptional repressor of proinflammatory cytokine gene expression. Our work identifies a critical molecular pathway regulating the pathogenic program of CD4 + T cells and brings new perspectives for potential therapies of autoimmune and inflammatory diseases.