A tissue-intrinsic IL-33/EGF circuit promotes epithelial regeneration after intestinal injury Journal Article
| Authors: | Calafiore, M.; Fu, Y. Y.; Vinci, P.; Arnhold, V.; Chang, W. Y.; Jansen, S. A.; Egorova, A.; Takashima, S.; Kuttiyara, J.; Ito, T.; Serody, J.; Nakae, S.; Turnquist, H.; van Es, J.; Clevers, H.; Lindemans, C. A.; Blazar, B. R.; Hanash, A. M. |
| Article Title: | A tissue-intrinsic IL-33/EGF circuit promotes epithelial regeneration after intestinal injury |
| Abstract: | Intestinal stem cells (ISCs) maintain the epithelial lining of the intestines, but mechanisms regulating ISCs and their niche after damage remain poorly understood. Utilizing radiation injury to model intestinal pathology, we report here that the Interleukin-33 (IL-33)/ST2 axis, an immunomodulatory pathway monitored clinically as an intestinal injury biomarker, regulates intrinsic epithelial regeneration by inducing production of epidermal growth factor (EGF). Three-dimensional imaging and lineage-specific RiboTag induction within the stem cell compartment indicated that ISCs expressed IL-33 in response to radiation injury. Neighboring Paneth cells responded to IL-33 by augmenting production of EGF, which promoted ISC recovery and epithelial regeneration. These findings reveal an unknown pathway of niche regulation and crypt regeneration whereby the niche responds dynamically upon injury and the stem cells orchestrate regeneration by regulating their niche. This regenerative circuit also highlights the breadth of IL-33 activity beyond immunomodulation and the therapeutic potential of EGF administration for treatment of intestinal injury. © 2023, Springer Nature Limited. |
| Keywords: | epidermal growth factor; controlled study; nonhuman; animal cell; animal tissue; gene expression; animal experiment; animal model; protein; tissue regeneration; in vivo study; pathology; radiation injury; disease severity; imaging, three-dimensional; radiation injuries; immunomodulation; stem cell niche; injury; intestine injury; growth rate; intestine crypt; paneth cell; receptor cross-talk; digestive system; intestine epithelium; intestinal stem cell; three-dimensional imaging; interleukin 33; cell component; humans; human; male; female; article; induced response; interleukin-33; interleukin 1 receptor like 1 protein; experimental radiation injury |
| Journal Title: | Nature Communications |
| Volume: | 14 |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2023-09-05 |
| Start Page: | 5411 |
| Language: | English |
| DOI: | 10.1038/s41467-023-40993-5 |
| PUBMED: | 37669929 |
| PROVIDER: | scopus |
| PMCID: | PMC10480426 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is Alan Hanash -- Source: Scopus |
