1. ¹Interdisciplinary Group of Molecular Immunopathology, Dermatology Medical, Immunology, University Hospital Charité, Berlin, Germany
2. ²Jerini AG, Berlin, Germany
3. ³Department of Dermatology, University Hospital Charité, Berlin, Germany
4. ⁴CRBA Dermatology, Schering AG, Berlin, Germany
5. ⁵Institute of Medical Immunology, University Hospital Charité, Berlin, Germany

Correspondence: Dr R Sabat, Interdisciplinary Group of Molecular Immunopathology, Dermatology/Medical Immunology, Campus—Charité Mitte, University Hospital Charité, Schumannstr. 20/21, D-10117 Berlin, Germany. E-mail: robert.sabat@charite.de

Received 20 July 2004; Revised 13 September 2004; Accepted 13 September 2004; Published online 4 November 2004.

Abstract

Interleukin(IL)-10 and IL-22 are structurally related cytokines. Their heterodimeric receptors consist of the cytokine-specific chains IL-10R1 and IL-22R1, respectively, and the common chain IL-10R2. This study focused on the question of whether IL-10 modulates IL-22 effects and vice versa. This question is important because IL-10 and IL-22 exert anti- and proinflammatory effects, respectively, and, as we show here, are simultaneously present in both systemic and local inflammation. The revealed lacking concomitance of IL-10R1 and IL-22R1 on identical cells excluded any possible interaction between IL-10 and IL-22 apart from the competition for IL-10R2. To study this competition, monocytes and hepatocytes were chosen. The dependence of the cytokine action on IL-10R2 was verified. Interestingly, no influence of IL-22 on IL-10 effects was observed. The same was true when IL-22 was used in complex with IL-22-binding protein. Similarly, no influence of IL-10 was found on IL-22 action. This missing competition seemed to be due to a lack of binding between IL-10R2 and the native cytokines in the absence of their corresponding R1 chain. However, IL-10R2 interacted with defined IL-10- and IL-22-derived peptides supporting the hypothesis that cytokine binding to its corresponding R1 chain creates a binding site on this cytokine for IL-10R2.