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

  • Suhyun Kim (Department of Biochemistry, Kangwon National University) ;
  • Eun-Hye Hong (Laboratory of Microbiology and Immunology, Department of Pharmacy, Kangwon National University) ;
  • Cheol-Ki Lee (Department of Biochemistry, Kangwon National University) ;
  • Yiseul Ryu (Institute of Life Sciences (ILS), Kangwon National University) ;
  • Hyunjin Jeong (Laboratory of Microbiology and Immunology, Department of Pharmacy, Kangwon National University) ;
  • Seungnyeong Heo (Department of Biochemistry, Kangwon National University) ;
  • Joong-Jae Lee (Department of Biochemistry, Kangwon National University) ;
  • Hyun-Jeong Ko (Laboratory of Microbiology and Immunology, Department of Pharmacy, Kangwon National University)
  • Received : 2021.11.15
  • Accepted : 2022.03.03
  • Published : 2022.06.30
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Abstract

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.

Keywords

Acknowledgement

This work was supported by the National Research Foundation (NRF) of Korea (2019R1I1A3A01047208, 2019R1I1A1A01058773, 2020R1A2B5B02001552, 2020R1A5A8019180, and 2020R1I1A1A01069947), and Kangwon National University (520190031).

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