Interleukin-10 regulates goblet cell numbers through Notch signaling in the developing zebrafish intestine
- Morales, R.A., Rabahi, S., Diaz, O.E., Salloum, Y., Kern, B.C., Westling, M., Luo, X., Parigi, S.M., Monasterio, G., Das, S., Hernández, P.P., Villablanca, E.J.
- Mucosal immunology 15(5): 940-951 (Journal)
- Registered Authors
- Das, Srustidhar, Diaz, Oscar E., Hernández-Cerda, Pedro, Luo, Xinxin, Morales, Rodrigo A., Rabahi, Soraya, Villablanca, Eduardo J.
- MeSH Terms
- Cell Count
- Cell Differentiation/genetics
- Goblet Cells*
- Intestinal Mucosa/metabolism
- Signal Transduction
- 35840681 Full text @ Mucosal Immunol
Morales, R.A., Rabahi, S., Diaz, O.E., Salloum, Y., Kern, B.C., Westling, M., Luo, X., Parigi, S.M., Monasterio, G., Das, S., Hernández, P.P., Villablanca, E.J. (2022) Interleukin-10 regulates goblet cell numbers through Notch signaling in the developing zebrafish intestine. Mucosal immunology. 15(5):940-951.
Cytokines are immunomodulatory proteins that orchestrate cellular networks in health and disease. Among these, interleukin (IL)-10 is critical for the establishment of intestinal homeostasis, as mutations in components of the IL-10 signaling pathway result in spontaneous colitis. Whether IL-10 plays other than immunomodulatory roles in the intestines is poorly understood. Here, we report that il10, il10ra, and il10rb are expressed in the zebrafish developing intestine as early as 3 days post fertilization. CRISPR/Cas9-generated il10-deficient zebrafish larvae showed an increased expression of pro-inflammatory genes and an increased number of intestinal goblet cells compared to WT larvae. Mechanistically, Il10 promotes Notch signaling in zebrafish intestinal epithelial cells, which in turn restricts goblet cell expansion. Using murine organoids, we showed that IL-10 modulates goblet cell frequencies in mammals, suggesting conservation across species. This study demonstrates a previously unappreciated IL-10-Notch axis regulating goblet cell homeostasis in the developing zebrafish intestine and may help explain the disease severity of IL-10 deficiency in the intestines of mammals.
Genes / Markers
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes