A soluble class II cytokine receptor, IL-22RA2, is a naturally occurring IL-22 antagonist

Xu, Wenfeng; Presnell, Scott; Parrish-Novak, Julia; Kindsvogel, Wayne; Jaspers, Steve; Chen, Zhi; Dillon, Stacey R.; Gao, Zeren; Gilbert, Teresa; Madden, Karen; Schlutsmeyer, Stacy; Yao, Lena; Whitmore, Theodore E.; Chandrasekher, Yasmin A.; Grant, Francis James; Maurer, Mark; Jelinek, Laura; Storey, H. H.; Brender, Ty; Hammond, Angie; Topouzis, Stavros; Clegg, Christopher H.; Foster, Donald C.

doi:10.1073/pnas.171303198

Cited by 196 publications

(155 citation statements)

References 27 publications

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“…IL-22BP is a soluble, nonsignaling single-chain receptor which specifically binds IL-22 and was shown to prevent its effect on IL-22-sensitive cells in vitro. [27][28][29][30] As IL-22BP may potentially favor IL-22 binding to IL-10R2, for example, by changing IL-22's structural conformation, we investigated whether IL-22, preincubated with IL-22BP at increasing molecular ratios (1 : 0.5 to 1 : 4), could modulate IL-10 effects. The activity of these IL-22BP concentrations was initially confirmed (see Materials and methods section).…”

Section: Simultaneous Presence Of Il-10 and Il-22 In Vivo?mentioning

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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Section: Simultaneous Presence Of Il-10 and Il-22 In Vivo?mentioning

confidence: 99%

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

Wolk

Witte

Reineke³

et al. 2004

Genes Immun

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“…Interference with the binding of IL-22 to their membrane receptors and, thus, inhibition of cytokine signaling has been demonstrated in vitro. [15][16][17] In order to investigate the interaction of IL-22 and its binding protein in an animal model in the future, we isolated both genomic and cDNA clones of mouse IL-22 binding protein (mIL-22BP) by homology screening and purified the mIL-22BP recombinant protein for functional assay. We demonstrated that mIL-22BP can neutralize STAT3 activation in two hepatoma cell lines (HepG2 and H4IIE) stimulated with either human or mouse IL-22.…”

Section: Introductionmentioning

confidence: 99%

Cloning and characterization of mouse IL-22 binding protein

Wei

Liang

et al. 2003

Genes Immun

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Interleukin-22 (IL-22), a member of IL-10 family, plays some important roles in immune response through activation of the STAT 3 signal transduction pathway. Two types of IL-22-binding receptor have been discovered, a membrane-bound receptor and a soluble receptor, both encoded by different genes. IL-22 may be involved in inflammatory processes specifically regulated by soluble receptors. By screening a mouse genomic library for a human IL-22 binding protein homologue, we identified the mouse genomic clone of IL-22 binding protein. Its coding sequence was verified and isolated by RT-PCR. The gene encodes a protein of 230 amino acids that share 67.1% amino-acid sequence identity with human IL-22 binding protein.We designated this receptor 'mouse IL-22 binding protein' (mIL-22BP). mIL-22BP could be upregulated by LPS stimulation in mouse monocytes. mIL-22BP binds to mouse and human IL-22 and neutralizes STAT3 activation induced by both cytokines in human and rat hepatoma cell lines. Treating B cells with mouse IL-22 induces production of reactive oxygen species, which mIL-22BP blocks.

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“…All IL-10 family members signal through the combination of a long chain (IL-10R1, IL-22R1, IL-20R1, or IFN-kR) and a short-chain (IL-10R2 or IL20-R2) class II cytokine receptor (reviewed in [143,145], Table 2). Additionally, IL-22 can interact with high affinity with the IL-22 binding protein (IL-22BP), a soluble type 1 receptor that can antagonizes IL-22 signaling by impairing its interaction with the transmembrane receptor IL-22R1 [147]; Fig. 3.…”

Section: Receptors Involved In Il-10 Family Members Signalingmentioning

confidence: 99%

“…The IL-22BP human gene is organized in six exons and located on chromosome 6, 100 kb apart from IL-20R1 and 24 kb from the gene encoding IFN-cR1 [147,154,155]. Tissue distribution of IL-22BP mRNA showed the highest expression levels in breast, placenta, and skin; but high expression was also found in spleen, gastrointestinal tract, and lungs, and lower levels were detected in brain, heart, thymus, pancreas, testis, and prostate [147,155].…”

Section: The Il-22/il-22bp Structure and Interfacesmentioning

confidence: 99%

“…Tissue distribution of IL-22BP mRNA showed the highest expression levels in breast, placenta, and skin; but high expression was also found in spleen, gastrointestinal tract, and lungs, and lower levels were detected in brain, heart, thymus, pancreas, testis, and prostate [147,155]. Nothing is currently known about the distribution of the protein, its concentration in various body fluids, and its correlation with pathophysiological processes.…”

Section: The Il-22/il-22bp Structure and Interfacesmentioning

confidence: 99%

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

Trivella

Ferreira-Junior

Dumoutier

et al. 2010

Cell. Mol. Life Sci.

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The IL-10 family of cytokines is comprised of IL-10, . The IL-10 family members bind to shared class II cytokine receptor chains that associate in various combinations in heterodimeric complexes. Upon interleukin/receptor complex formation, these proteins switch on the Jak/STAT pathway and elicit pleiotropic biological responses whose variety sharply contrasts with their structural similarities. IL-10 family members are involved in several human diseases and health conditions and hence their structural analyses may provide valuable information to design specific therapeutic strategies. In this review, we describe the human interleukin-10 family of cytokines, focusing on their structures and functions, with particular attention given to IL-22 and IL-10. We report on the recently published structures of IL-10 cytokine family members and their complexes with cognate transmembrane and soluble receptors as well as on interleukin physiology and physiopathology.

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A soluble class II cytokine receptor, IL-22RA2, is a naturally occurring IL-22 antagonist

Cited by 196 publications

References 27 publications

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

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

Cloning and characterization of mouse IL-22 binding protein

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

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