Kim Suhyun, Hong Eun-Hye, Lee Cheol-Ki, Ryu Yiseul, Jeong Hyunjin, Heo Seungnyeong, Lee Joong-Jae, Ko Hyun-Jeong
Department of Biochemistry, Kangwon National University, Chuncheon 24341, Korea.
Laboratory of Microbiology and Immunology, Department of Pharmacy, Kangwon National University, Chuncheon 24341, Korea.
Immune Netw. 2022 Mar 30;22(3):e26. doi: 10.4110/in.2022.22.e26. eCollection 2022 Jun.
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.
白细胞介素-22（IL-22）是一种多效性细胞因子，已知其对受损肠道屏障的再生具有深远影响。IL-22的组织保护特性有望在结肠炎的减轻和治疗中得到潜在应用。然而，由于IL-22在慢性炎症中具有促进疾病的作用，因此需要进行全面评估才能将IL-22应用于临床领域。在此，我们展示了在细菌中有效生产可溶性人IL-22，以证明重组IL-22是否具有改善结肠炎和炎症的能力。IL-22以生物活性单体和无功能寡聚体的形式表达。单体IL-22（mIL-22）通过一系列3种单独的色谱方法和酶促反应进行了高度纯化。我们发现，所得的mIL-22正确折叠，并且能够在HT-29细胞中磷酸化信号转导和转录激活因子3（STAT3）。随后，我们证明mIL-22能够减轻葡聚糖硫酸钠诱导的小鼠急性结肠炎，并抑制促炎细胞因子的产生。总体而言，我们的结果表明，重组mIL-22适合研究内源性IL-22在免疫反应中的生物学作用，并可开发为与炎症性疾病相关的生物制剂。
