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Induction of IL-4 Expression in CD4⁺ T Cells by Thymic Stromal Lymphopoietin¹

Miyuki Omori^* and Steven Ziegler^2,*,

^* Immunology Program, Benaroya Research Institute at Virginia Mason, Seattle, WA 98101; and Department of Immunology, University of Washington, Seattle, WA 98195

The cytokine thymic stromal lymphopoietin (TSLP) has been implicated in the development and progression of allergic inflammation in both humans and mice. Although the underlying mechanism is not known, TSLP-stimulated dendritic cells have been shown to prime human CD4⁺ T cells into Th2 cytokine-producing cells. However, its direct effect on CD4⁺ T cells has not been extensively investigated. In this study, we show that TSLP can drive Th2 differentiation in the absence of exogenous IL-4 and APCs. IL-4 blockade inhibited TSLP-mediated Th2 differentiation, demonstrating that IL-4 is involved in this process. Further analysis has shown that TSLP-induced Th2 differentiation is dependent on Stat6 and independent of IL-2 and that TSLP treatment leads to immediate, direct Il-4 gene transcription. Taken together, these data demonstrate that TSLP is directly involved in Th2-mediated responses via the induction of IL-4 production.

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 by National Institutes of Health Grant AI44259 (to S.Z.) and Johnson & Johnson Skin Research Training Grant (to M.O.).

² Address correspondence and reprint requests to Dr. Steven Ziegler, Immunology Program, Benaroya Research Institute at Virginia Mason, 1201 Ninth Avenue, Seattle, WA 98101. E-mail address: sziegler{at}benaroyaresearch.org

³ Abbreviations used in this paper: TSLP, thymic stromal lymphopoietin; TSLPR, TSLP receptor; phospho-Stat5, phosphorylated Stat5.

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