Preparation and characterization of mouse IL-22 and its four single-amino-acid muteins that act as IL-22 receptor-1 antagonists

Niv-Spector, Leonora; Shpilman, Michal; Levi-Bober, Mariela; Katz, Mark N.; Varol, Chen; Elinav, Eran; Gertler, Arieh

doi:10.1093/protein/gzs030

Cited by 10 publications

(6 citation statements)

References 34 publications

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“…This may be due to the insufficient function of IL-22 by the inhibition of IL-22 binding protein (IL-22BP), a natural antagonist of IL-22, suggesting that extremely large amount of IL-22 may be required to overcome the IL-22BP-mediated inhibition. [7,30,38,44] Indeed, several reports suggested that administration of IL-22 or IL-22Fc fusion protein exhibited sufficient protection against DSS-induced colitis in preclinical models. [15,45,46] On the contrary, however, blockade of IL-22 by neutralization antibody improved colitis induced by agonist anti-CD40 Ab or DNBS, suggesting complex role of IL-22 in intestinal inflammation and barrier function.…”

Section: Discussionmentioning

confidence: 99%

Amelioration of DSS-induced Acute Colitis in Mice by Recombinant Monomeric Human Interleukin-22

Hong

et al. 2021

Preprint

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Interleukin-22 (IL-22), a pleiotropic cytokine, is known to have a profound effect on the regeneration of damaged intestinal barriers. The tissue-protective properties of IL-22 are expected to be potentially exploited in the attenuation and treatment of colitis. However, because of the disease-promoting role of IL-22 in chronic inflammation, a comprehensive evaluation is required to translate IL-22 into the clinical domain. Here, we present the effective production of soluble human IL-22 in bacteria to prove whether recombinant IL-22 has the ability to ameliorate colitis and inflammation. IL-22 was expressed in the form of a biologically active monomer and a non-functional dimer. Monomeric IL-22 (mIL-22) was highly purified through a series of three separate chromatographic methods and an enzymatic reaction. We reveal that the resulting mIL-22 is correctly folded and is able to phosphorylate signal transducer and activator of transcription 3 in HT-29 cells. Subsequently, we demonstrate that mIL-22 enables the attenuation of dextran sodium sulfate-induced acute colitis in mice, as well as the suppression of pro-inflammatory cytokine production. Collectively, our results suggest that the recombinant mIL-22 is suitable to study the biological roles of endogenous IL-22 in immune responses and can be developed as a biological agent associated with inflammatory disorders.

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Section: Discussionmentioning

confidence: 99%

Amelioration of DSS-induced Acute Colitis in Mice by Recombinant Monomeric Human Interleukin-22

Hong

et al. 2021

Preprint

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“…Notably, there is up‐regulation of IFN‐β in the inflamed synovium of patients with rheumatoid arthritis (van Holten et al ., ). Altogether, it is tempting to speculate that reduction of IL‐22 biological activity by neutralizing antibodies, IL‐22BP or antagonistic IL‐22 muteins (Niv‐Spector et al ., ) would reduce signs of inflammation and disease severity in psoriasis and rheumatoid arthritis patients. The development of antagonistic IL‐22 muteins (Niv‐Spector et al ., ) is particularly promising, for instance, in psoriasis.…”

Section: Restrictions Of Il‐22 Usage For Tissue‐protective Therapymentioning

confidence: 99%

“…Altogether, it is tempting to speculate that reduction of IL‐22 biological activity by neutralizing antibodies, IL‐22BP or antagonistic IL‐22 muteins (Niv‐Spector et al ., ) would reduce signs of inflammation and disease severity in psoriasis and rheumatoid arthritis patients. The development of antagonistic IL‐22 muteins (Niv‐Spector et al ., ) is particularly promising, for instance, in psoriasis. These artificial analogues of IL‐22, generated by introduction of mutations, are able to bind to IL‐22 receptor chain‐1 with high affinity, but because they do not also recruit the IL‐10 receptor chain‐2, are unable to initiate IL‐22 signal transduction.…”

Section: Restrictions Of Il‐22 Usage For Tissue‐protective Therapymentioning

confidence: 99%

IL‐22 in tissue‐protective therapy

Mühl

Scheiermann

Bachmann

et al. 2013

British J Pharmacology

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IL‐22, a member of the IL‐10 cytokine family, has recently gained significant attention as a protective agent in murine models of diseases driven by epithelial injury. Like its biochemical and functional sibling IL‐10, IL‐22 elicits cellular activation primarily by engaging the STAT3 signalling pathway. Exclusively produced by leukocytes, but targeting mostly cells of epithelial origin, IL‐22 has been proposed as a specialized cytokine messenger acting between leukocytic and non‐leukocytic cell compartments. A lack of response in leukocytes to IL‐22 mirrors tightly controlled IL‐22 receptor expression and probably explains the apparent lack of instant adverse effects after systemic IL‐22 administration to mice. Anti‐apoptotic, pro‐proliferative and pro‐regenerative characteristics the major biological properties of this cytokine. Specifically, application of IL‐22 is associated with tissue protection and/or regeneration in murine models of infection/microbe‐driven inflammation at host/environment interfaces, ventilator‐induced lung injury, pancreatitis and liver damage. Overall, preclinical studies would support therapeutic administration of seemingly well‐tolerated recombinant IL‐22 for treatment of an array of acute diseases manifested in epithelial tissues. However, the feasibility of prolonged administration of this cytokine is expected to be restricted by the tumourigenic potential of the IL‐22/STAT3 axis. IL‐22, moreover, apparently displays an inherent context‐specific capacity to amplify distinct aspects of autoimmune inflammation. Here, the prospects, expectations and restrictions of IL‐22 administration in tissue‐protective therapy are discussed.

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“…Despite the clinical significance of IL-22, the effective production of human recombinant IL-22 (hrIL-22) in bacteria has not yet been established. Therefore, recombinant IL-22 (rIL-22) has been mainly obtained by a refolding method from bacterial inclusion bodies due to its extremely low solubility ( 26 27 ). Moreover, because the renaturation process is a complex and labor-intensive procedure, it is difficult to optimize and perform at a laboratory scale for research purposes ( 28 ).…”

Section: Introductionmentioning

confidence: 99%

Amelioration of DSS-Induced Acute Colitis in Mice by Recombinant Monomeric Human Interleukin-22

et al. 2022

View full text Add to dashboard Cite

IL-22, a pleiotropic cytokine, is known to have a profound effect on the regeneration of damaged intestinal barriers. The tissue-protective properties of IL-22 are expected to be potentially exploited in the attenuation and treatment of colitis. However, because of the disease-promoting role of IL-22 in chronic inflammation, a comprehensive evaluation is required to translate IL-22 into the clinical domain. Here, we present the effective production of soluble human IL-22 in bacteria to prove whether recombinant IL-22 has the ability to ameliorate colitis and inflammation. IL-22 was expressed in the form of a biologically active monomer and non-functional oligomers. Monomeric IL-22 (mIL-22) was highly purified through a series of 3 separate chromatographic methods and an enzymatic reaction. We reveal that the resulting mIL-22 is correctly folded and is able to phosphorylate STAT3 in HT-29 cells. Subsequently, we demonstrate that mIL-22 enables the attenuation of dextran sodium sulfate-induced acute colitis in mice, as well as the suppression of pro-inflammatory cytokine production. Collectively, our results suggest that the recombinant mIL-22 is suitable to study the biological roles of endogenous IL-22 in immune responses and can be developed as a biological agent associated with inflammatory disorders.

show abstract

Preparation and characterization of mouse IL-22 and its four single-amino-acid muteins that act as IL-22 receptor-1 antagonists

Cited by 10 publications

References 34 publications

Amelioration of DSS-induced Acute Colitis in Mice by Recombinant Monomeric Human Interleukin-22

Amelioration of DSS-induced Acute Colitis in Mice by Recombinant Monomeric Human Interleukin-22

IL‐22 in tissue‐protective therapy

Amelioration of DSS-Induced Acute Colitis in Mice by Recombinant Monomeric Human Interleukin-22

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