Il22, interleukin-22, is a cytokine crucial for epithelial homeostasis. It plays a role in multiple aspects of epithelial barrier function, such as regulating epithelial cell growth, permeability, mucus and antimicrobial protein production, and complement production [2]. It has been associated with signaling pathways like STAT3, and its dysregulation can impact various biological processes and disease states [4,5]. Genetic models, including KO/CKO mouse models, are valuable for studying its functions.

High levels of Il22 in ileal mouse organoids decreased their survival, though resistant ones grew larger. In vivo, increased Il22 limited intestinal stem cell (ISC) expansion, favoring transit-amplifying (TA) progenitor cell expansion [1]. In a murine model of colitis, Il22Ra1 signaling in MATH1+ cells (goblet and progenitor cells) was essential for maintaining the mucosal barrier and intestinal tissue regeneration, promoting mucin core-2 O-glycan extension [6]. In allogeneic stem cell transplantation in humans, low intestinal Il22 was associated with increased transplant-related mortality [3].

In conclusion, Il22 is essential for epithelial homeostasis and tissue repair in the intestine. Mouse models have revealed its role in regulating cell expansion in the ileum and its importance in maintaining the mucosal barrier during colitis. In the context of allogeneic stem cell transplantation, Il22 levels are associated with patient prognosis, highlighting its significance in these disease areas.

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. 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/

3. 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/

4. Cui, Xiangrong, Jing, Xuan, Yi, Qin, Tan, Bin, Zhu, Jing. 2019. IL22 furthers malignant transformation of rat mesenchymal stem cells, possibly in association with IL22RA1/STAT3 signaling. In Oncology reports, 41, 2148-2158. doi:10.3892/or.2019.7007. https://pubmed.ncbi.nlm.nih.gov/30816520/

5. 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/

6. Singh, Ankita, Beaupre, Michael, Villegas-Novoa, Cecilia, Allbritton, Nancy L, Kumar, Pawan. 2024. IL-22 promotes mucin-type O-glycosylation and MATH1+ cell-mediated amelioration of intestinal inflammation. In Cell reports, 43, 114206. doi:10.1016/j.celrep.2024.114206. https://pubmed.ncbi.nlm.nih.gov/38733584/