CD4 <sup>+</sup> T cells require Ikaros to inhibit their differentiation toward a pathogenic cell fate
Chiara Bernardi, Gaëtan Maurer, Tao Ye, Patricia Marchal, Bernard Jost, Manuela Wissler, Ulrich Maurer, Philippe Kastner, Susan Chan, Céline Charvet
Abstract
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.