Il22, interleukin-22, is a critical cytokine in regulating epithelial homeostasis. It is involved in multiple aspects of epithelial barrier function, such as regulating epithelial cell growth, permeability, mucus and antimicrobial protein production, and complement production [3]. It has been associated with signaling pathways like STAT3, and its dysregulation can impact various biological processes and disease states [4]. Genetic models, especially KO/CKO mouse models, are valuable for studying its functions.

In an ileal organoid model, high IL22 levels decreased ileal organoid survival, reduced ISC biomarker expression and self-renewal-associated pathway activity, and inhibited ISC expansion, while promoting TA progenitor cell expansion [1]. In allogeneic stem cell transplantation patients, low intestinal IL22 was associated with increased transplant-related mortality, and its expression seemed microbiota-dependent [2]. In colonic epithelial cells, AhR is required for optimal IL22 signaling, as AhR KO reduced responsiveness to IL22 due to enhanced SOCS3 expression [4].

In conclusion, Il22 plays an essential role in maintaining epithelial homeostasis, especially in the intestine. Model-based research, particularly KO/CKO mouse models, has revealed its significance in diseases like inflammatory bowel disease, graft-versus-host disease, and cancer, providing insights into its role in disease mechanisms and potential therapeutic targets.

References:

1. Zwarycz, Bailey, Gracz, Adam D, Rivera, Kristina R, Zhao, Qihong, Magness, Scott T. 2018. IL22 Inhibits Epithelial Stem Cell Expansion in an Ileal Organoid Model. In Cellular and molecular gastroenterology and hepatology, 7, 1-17. doi:10.1016/j.jcmgh.2018.06.008. https://pubmed.ncbi.nlm.nih.gov/30364840/

2. Ghimire, Sakhila, Ederer, Katharina U, Meedt, Elisabeth, Holler, Ernst, Bülow, Sigrid. 2022. Low Intestinal IL22 Associates With Increased Transplant-Related Mortality After Allogeneic Stem Cell Transplantation. In Frontiers in immunology, 13, 857400. doi:10.3389/fimmu.2022.857400. https://pubmed.ncbi.nlm.nih.gov/35572572/

3. Keir, Mary, Yi, Tangsheng, Lu, Timothy, Ghilardi, Nico. 2020. The role of IL-22 in intestinal health and disease. In The Journal of experimental medicine, 217, e20192195. doi:10.1084/jem.20192195. https://pubmed.ncbi.nlm.nih.gov/32997932/

4. Han, Huajun, Davidson, Laurie A, Fan, Yang-Yi, Safe, Stephen H, Chapkin, Robert S. 2021. Loss of aryl hydrocarbon receptor suppresses the response of colonic epithelial cells to IL22 signaling by upregulating SOCS3. In American journal of physiology. Gastrointestinal and liver physiology, 322, G93-G106. doi:10.1152/ajpgi.00074.2021. https://pubmed.ncbi.nlm.nih.gov/34755534/