Open AccessCD4+T cells require Ikaros to inhibit their differentiation toward a pathogenic cell fate
Author(s) -
Chiara Bernardi,
Gaëtan Maurer,
Tao Ye,
Patricia Marchal,
Bernard Jost,
Manuela Wissler,
Ulrich Maurer,
Philippe Kastner,
Susan Chan,
Céline Charvet
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2023172118
Subject(s) - chromatin , biology , t cell receptor , transcription factor , microbiology and biotechnology , enhancer , t cell , jurkat cells , cd28 , zap70 , stat5 , gene , signal transduction , genetics , immune system
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.