气候变化领域集成服务门户(CCPortal): CD4+ T cells require Ikaros to inhibit their differentiation toward a pathogenic cell fate

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DOI	10.1073/pnas.2023172118
	CD4+ T cells require Ikaros to inhibit their differentiation toward a pathogenic cell fate
	Bernardi C.; Maurer G.; Ye T.; Marchal P.; Jost B.; Wissler M.; Maurer U.; Kastner P.; Chan S.; Charvet C.
发表日期	2021
ISSN	00278424
卷号	118 期号:17
英文摘要	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. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	GM-CSF; Ikaros; IL-17; Pathogenicity; Proinflammatory cytokines
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/179744
作者单位	Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, 67404, France; Centre National de la Recherche Scientifique, UMR7104, Illkirch, 67404, France; Institut National de la Santé et de la Recherche Médicale, U1258, Illkirch, 67404, France; Université de Strasbourg, Strasbourg, 67000, France; Plateforme GenomEast, Infrastructure France Génomique, Illkirch, 67404, France; Institute of Molecular Medicine and Cell Research, Albert-Ludwigs-University of Freiburg, Freiburg, 79104, Germany; Spemann Graduate School of Biology and Medicine, Albert-Ludwigs-University of Freiburg, Freiburg, 79104, Germany; BIOSS, Centre for Biological Signalling Studies, Freiburg, 79104, Germany; Faculté de Médecine, Université de Strasbourg, Strasbourg, 67000, France
推荐引用方式 GB/T 7714	Bernardi C.,Maurer G.,Ye T.,et al. CD4+ T cells require Ikaros to inhibit their differentiation toward a pathogenic cell fate[J],2021,118(17).
APA	Bernardi C..,Maurer G..,Ye T..,Marchal P..,Jost B..,...&Charvet C..(2021).CD4+ T cells require Ikaros to inhibit their differentiation toward a pathogenic cell fate.Proceedings of the National Academy of Sciences of the United States of America,118(17).
MLA	Bernardi C.,et al."CD4+ T cells require Ikaros to inhibit their differentiation toward a pathogenic cell fate".Proceedings of the National Academy of Sciences of the United States of America 118.17(2021).