Temporal associations between interleukin 22 and the extracellular domains of IL-22R and IL-10R2

Li, Jing; Tomkinson, Kathy N.; Tan, Xiang-Yang; Wu, Paul W.; Yan, Grace; Spaulding, Vikki; Deng, Bijia; Annis-Freeman, Bethany; Heveron, Kathleen; Zollner, Ricardo de Lima; Zutter, Gerard De; Wright, Jill F.; Crawford, Tara K.; Liu, Wei; Jacobs, Kenneth; Wolfman, Neil M.; Ling, Vincent; Pittman, Debra D.; Veldman, Geertruida M.; Fouser, Lynette A.

doi:10.1016/j.intimp.2004.01.010

Cited by 57 publications

(58 citation statements)

References 29 publications

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“…B6129SF2/J mice (n ϭ 10) were dosed orally with vehicle (2% Tween 80, 0.5% methylcellulose), WYE-151650, or CP-690,550, or intraperitoneally with anti-IL-22 antibody (generated internally, clone Ab-01) (19). One hour later, mice were injected intraperitoneally with 10 g of recombinant mouse IL-22 (20). Six hours later, mice were bled, and serum SAA levels were measured by enzyme-linked immunosorbent assay (ELISA; BioSource).…”

Section: Compounds and Reagentsmentioning

confidence: 99%

Selective functional inhibition of JAK‐3 is sufficient for efficacy in collagen‐induced arthritis in mice

Lin

Hegen

Quadros

et al. 2010

Arthritis & Rheumatism

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Objective. All ␥-chain cytokines signal through JAK-3 and JAK-1 acting in tandem. We undertook this study to determine whether the JAK-3 selective inhibitor WYE-151650 would be sufficient to disrupt cytokine signaling and to ameliorate autoimmune disease pathology without inhibiting other pathways mediated by JAK-1, JAK-2, and Tyk-2.Methods. JAK-3 kinase selective compounds were characterized by kinase assay and JAK-3-dependent (interleukin-2 [IL-2]) and -independent (IL-6, granulocyte-macrophage colony-stimulating factor [GM-CSF]) cell-based assays measuring proliferation or STAT phosphorylation. In vivo, off-target signaling was measured by IL-22-and erythropoietin (EPO)-mediated models, while on-target signaling was measured by IL-2-mediated signaling. Efficacy of JAK-3 inhibitors was determined using delayed-type hypersensitivity (DTH) and collagen-induced arthritis (CIA) models in mice.Results. In vitro, WYE-151650 potently suppressed IL-2-induced STAT-5 phosphorylation and cell proliferation, while exhibiting 10-29-fold less activity against JAK-3-independent IL-6-or GM-CSF-induced STAT phosphorylation. Ex vivo, WYE-151650 suppressed IL-2-induced STAT phosphorylation, but not IL-6-induced STAT phosphorylation, as measured in whole blood. In vivo, WYE-151650 inhibited JAK-3-mediated IL-2-induced interferon-␥ production and decreased the natural killer cell population in mice, while not affecting IL-22-induced serum amyloid A production or EPO-induced reticulocytosis. WYE-151650 was efficacious in mouse DTH and CIA models.Conclusion. In vitro, ex vivo, and in vivo assays demonstrate that WYE-151650 is efficacious in mouse CIA despite JAK-3 selectivity. These data question the need to broadly inhibit JAK-1-, JAK-2-, or Tyk-2-dependent cytokine pathways for efficacy.

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Section: Compounds and Reagentsmentioning

confidence: 99%

Selective functional inhibition of JAK‐3 is sufficient for efficacy in collagen‐induced arthritis in mice

Lin

Hegen

Quadros

et al. 2010

Arthritis & Rheumatism

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“…40 Very recently, Fouser's group has also shown that biotinylated IL-22 binds IL-22R1-Fc homodimer but not IL-10R2-Fc homodimer in an ELISA-based format, and that IL-10R2 stabilizes the association of IL-22 with IL-22R1. 42 Interestingly, binding of, for example, monoclonal Abs to defined areas of IL-10 or IL-22 increased the following binding of other proteins to these cytokines. 39,42 This is further evidence that the binding of ligands can result in a conformational change of the IL-10 and the IL-22 molecule.…”

Section: Modulation Of the Il-22 Effect By The Presence Of Il-10mentioning

confidence: 99%

“…42 Interestingly, binding of, for example, monoclonal Abs to defined areas of IL-10 or IL-22 increased the following binding of other proteins to these cytokines. 39,42 This is further evidence that the binding of ligands can result in a conformational change of the IL-10 and the IL-22 molecule. If this is the case, our data would imply that such a conformational change of IL-22 can not be achieved through its prior binding to IL-22BP (Figure 3b) Another theoretical possibility for the lacking interference between IL-10 and IL-22 might be that IL-10 and IL-22 use different binding sites on IL-10R2.…”

Section: Modulation Of the Il-22 Effect By The Presence Of Il-10mentioning

confidence: 99%

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

Wolk

Witte

Reineke³

et al. 2004

Genes Immun

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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.

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“…It also upregulates pancreatitis-associated protein 1 (PAP1) and osteopontin, which may have protective or trophic effects during inflammation, in pancreatic acinar cells [17,19,20]. In addition to its cellular receptor, IL-22 binds to soluble IL-22-binding protein (IL-22BP), which is a secreted member of the class II cytokine receptor family and appears to act as a natural antagonist for IL-22 [21][22][23][24].…”

Section: Introductionmentioning

confidence: 99%

Regulation of T cells and cytokines by the interleukin‐10 (IL‐10)‐family cytokines IL‐19, IL‐20, IL‐22, IL‐24 andIL‐26

Kotenko²,

et al. 2006

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The family of IL-10-related cytokines includes several human members, , and a series of herpesviral and poxviral paralogs. Some of these cytokines share common receptor subunits. In this study, we investigated the effects of these cytokines on naive T cell differentiation, antigen-specific T cell suppression, survival and expression of surface markers in comparison to IL-10 and cytomegalovirus (CMV)-IL-10. Human CD45RA + T cells were stimulated in the presence of IL-10-family cytokines in sequential 12-day cycles.

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Temporal associations between interleukin 22 and the extracellular domains of IL-22R and IL-10R2

Cited by 57 publications

References 29 publications

Selective functional inhibition of JAK‐3 is sufficient for efficacy in collagen‐induced arthritis in mice

Selective functional inhibition of JAK‐3 is sufficient for efficacy in collagen‐induced arthritis in mice

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

Regulation of T cells and cytokines by the interleukin‐10 (IL‐10)‐family cytokines IL‐19, IL‐20, IL‐22, IL‐24 andIL‐26

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