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. The Journal of Immunology, 2009, 182: 741-745.