Cutting edge: Ikaros is a regulator of Th2 cell differentiation.
Ikaros, a hematopoietic transcription factor, has well defined effects on early lymphocyte development in the bone marrow and thymus. In this study we demonstrate that Ikaros is a positive regulator of Th2 cytokine gene expression in peripheral T cells. CD4+ T cells from naive Ikaros(null) mice cultured under Th2-skewing conditions express the Th1 cytokine IFN-gamma and have reduced IL-4, IL-5, and IL-13 expression. Ikaros directly associates with several Th2 locus regulatory regions in naive CD4+ T cells. The decreased ability to express Th2 cytokines in Ikaros(null)T cells corresponds with histone 3 hypoacetylation across the Th2 cytokine locus as well as decreased GATA3 and cMaf and increased T-bet and STAT1 expression. These data support a model whereby Ikaros directly activates Th2 gene expression by promoting local chromatin accessibility during CD4+ T cell differentiation and also acts indirectly to regulate expression of Th2- and Th1-specific transcription factors.
Quirion
Mary R
MR
Department of Microbiology and Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Gregory
Gregory D
GD
Umetsu
Sarah E
SE
Winandy
Susan
S
Brown
Melissa A
MA
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D006410:Hematopoiesis / Q000235:genetics / Q000276:immunology; D051740:Ikaros Transcription Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018448:Models, Immunological; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D015533:Transcriptional Activation / Q000276:immunology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology*
D002843:Chromatin; C497238:Zfpn1a1 protein, mouse; D051740:Ikaros Transcription Factor; D007371:Interferon-gamma