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

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.

Aberrant expression of IL-22 receptor 1 and autocrine IL-22 stimulation contribute to tumorigenicity in ALK+ anaplastic large cell lymphoma

“…28,29 IL-22R1 is characteristically absent in benign immune cells including lymphocytes [16][17][18] in various epithelial cell lines, IL-22 has been shown to promote cell proliferation and activate a number of signaling pathways including those of STAT3, MAPK and AKT. 22,30 It is currently believed that the physiological function of IL-22 is related to the maintenance of innate immunity.…”

“…IL-10R2 is ubiquitously expressed, whereas IL-22R1 expression is restricted and not detectable in normal immune cells including B and T cells. [16][17][18] IL-22 stimulation is known to be negatively regulated by the IL-22-binding protein (IL-22BP), a naturally occurring decoy that can antagonize IL-22 binding to its receptor. [19][20][21] Once bound to its receptor, IL-22 is known to activate a number of signaling pathways including that of STAT3 and mitogen-activated protein kinase (MAPK).…”

Structure and function of interleukin-22 and other members of the interleukin-10 family

“…Although the overall IL-10R2 binding interfaces at the IL-22 and IL-10 ternary complexes are similar, the molecular details are quite different [160]. It appears that site 2b is the most important IL-10R2 interface in IL-10 ternary complex; whereas site 2a is central for IL-22 ternary complex formation [153].…”

The expression of legumain, an asparaginyl endopeptidase that controls antigen processing, is reduced in endotoxin-tolerant monocytes

“…mRNA expression was analyzed by real-time RT-PCR using the TaqMant system (Applied Biosystems, Weiterstadt, Germany) as described previously. 13,34,35 (a) mRNA expression of legumain, cathepsin B, cathepsin H, cathepsin L, cathepsin F and cathepsin S was analyzed in freshly isolated monocytes. Individual data obtained from six donors are indicated.…”

“…Legumain mRNA expression was analyzed by real-time RT-PCR using the TaqMant system (Applied Biosystems, Weiterstadt, Germany) as described previously. 13,34,35 Data from six participants per group are given as mean7s.e. Significance of the difference between LPS-primed and control groups was tested by Mann-Whitney U-test (*Po0.05).…”