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IL-20 Receptor 2 Signaling Down-Regulates Antigen-Specific T Cell Responses¹

Christian Wahl^*, Werner Müller^2,, Frank Leithäuser, Guido Adler^*, Franz Oswald^*, Jörg Reimann^*, Reinhold Schirmbeck^*, Anne Seier, Johannes Martin Weiss, Blair Prochnow and Ursula Maria Wegenka^3,*

^* University Medical Center, Center of Internal Medicine, Department of Internal Medicine I, Ulm, Germany; Department of Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany; and Department of Pathology and Department of Dermatology and Allergic Diseases, University Medical Center, Ulm, Germany

The recently described cytokines IL-19, IL-20, and IL-24 share structural homology with IL-10 and are therefore classified as members of the IL-10 family of cytokines. Although it has long been speculated that signaling by their heterodimeric receptor complexes (IL-20R1/IL-20R2 and IL-22R/IL-20R2) influences immunological processes, the target cells for this group of cytokines are still unclear. By generating a knockout mouse strain deficient for the common IL-20R β-chain (IL-20R2), we show that IFN- and IL-2 secretion is significantly elevated after stimulation of IL-20R2^–/–-deficient CD8 and CD4 T cells with Con A or anti-CD3/CD28 in vitro. IL-10 secretion by activated IL-20R2^–/– CD4 cells was diminished. Consistent with our in vitro results, significantly more Ag-specific CD8 IFN-⁺ and CD4 IFN-⁺ T cells developed to locally applied DNA vaccines in IL-20R2-deficient mice. In a T cell-dependent model of contact hypersensitivity, IL-20R2 knockout mice were more sensitive to the contact allergen trinitro-chloro-benzene. Thus, IL-20R2 signaling directly regulates CD8 and CD4 T cell answers in vitro and in vivo. For the first time, we provide evidence that IL-19, IL-20, and IL-24 are part of a signaling network that normally down-modulates T cell responses in mice.

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 a grant from Deutsche Forschungsgemeinschaft (DFG WE 3550/3-1) to U.M.W. and a DFG grant to F.O. (SFB 518/A18). Funding for W.M. was via Nationales Genomforschungsnetz.

² Current address: Bill Ford Chair in Cellular Immunology, University of Manchester, Faculty of Life Sciences, Manchester, U.K.

³ Address correspondence and reprint requests to Dr. Ursula Maria Wegenka, Robert Koch Strasse 8, D-89081 Ulm, Germany. E-mail address: ursula.wegenka{at}uniklinik-ulm.de

⁴ Abbreviations used in this paper: DC, dendritic cell; BFA, brefeldin A; CHS, contact hypersensitivity; ES, embryonic stem; FCM, flow cytometry; HBsAg, hepatitis B surface Ag; i.d., intradermal; mIL, murine IL; TNCB, trinitro-chloro-benzene.

⁵ The online version of this article contains supplementary material.

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