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Cutting Edge: Ikaros Is a Regulator of Th2 Cell Differentiation¹

Department of Microbiology and Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611

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- 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 costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported in part by National Institutes of Health Grants F31 NS058941 (to M.R.Q.), F30 ES015971 (to S.U.), and CA047992 (to M.A.B.).

² Current address: Department of Hematology, The Children’s Hospital of Philadelphia, Abramson Research Center, Room 315, 3615 Civic Center Boulevard, Philadelphia, PA 19104-4318.

³ Address correspondence and reprint requests to Dr. Melissa A. Brown, Department of Microbiology and Immunology, Northwestern University Feinberg School of Medicine, 6-701 Tarry Building, 320 East Superior Avenue, Chicago, IL 60611. E-mail address: m-brown12{at}northwestern.edu

⁴ Abbreviations used in this paper: H3, histone 3; ChIP, chromatin immunoprecipitation; CNS, conserved noncoding sequence; Ct, cycle threshold; Ik-7, Ikaros 7.

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