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Imidazoquinoline Acts as Immune Adjuvant for Functional Alteration of Thymic Stromal Lymphopoietin-Mediated Allergic T Cell Response¹

First Department of Internal Medicine, Kansai Medical University, Osaka, Japan

Atopic dermatitis is a major allergic disease that develops through dysregulation of Th2-mediated inflammation. Although dendritic cells (DCs) have been thought to play a critical role in the upstream phase of the allergic cascade, conventional drugs such as steroids and chemical mediator antagonists target the effector cells or factors in allergic inflammation. Recently, it has been demonstrated that interaction between thymic stromal lymphopoietin (TSLP) and human DCs plays an essential role in evoking inflammatory Th2 responses in allergy through OX40 ligand expression on DCs. In this study, we provide evidence that R848, an imidazoquinoline compound, which is a TLR ligand and a strong Th1 response-inducing reagent, is a potent adjuvant for the alteration of the Th2-inducing potency of human DCs activated by TSLP (TSLP-DCs). R848 inhibited the inflammatory Th2-inducing capacity of TSLP-DCs and redirected them to possessing an IL-10 and IFN--producing regulatory Th1-inducing capacity. This functional alteration depended on both repression of OX40 ligand expression and induction of IL-12 production from DCs by the addition of R848. Additionally, R848 had the ability to inhibit the TSLP-mediated expansion and maintenance of the Th2 memory response. These findings suggest that imidazoquinoline may be a useful in the treatment of allergic diseases that are triggered by TSLP.

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 Takeda Science Foundation, the Nakatomi Foundation, and a grant from The Ministry of Education, Culture, Sports, Science, and Technology of Japan (RR2002).

² Address correspondence and reprint requests to Dr. Tomoki Ito, First Department of Internal Medicine, Kansai Medical University, 10-15, Fumizono-Cho, Moriguchi-City, Osaka, 570-8506, Japan. E-mail address: itot{at}takii.kmu.ac.jp

³ Abbreviations used in this paper: TSLP, thymic stromal lymphopoietin; CBA, cytometric beads array; DC, dendritic cell; OX40L, OX40 ligand; PGN, peptidoglycan; p-stat5, phosphorylated stat5.