Is there an interaction between interleukin-10 and interleukin-22?

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.