2022-09-01
Optimized human intestinal organoid model reveals interleukin-22-dependency of paneth cell formation
Publication
Publication
Cell Stem Cell , Volume 29 - Issue 9 p. 1333- 1345.e6
Opposing roles have been proposed for IL-22 in intestinal pathophysiology. We have optimized human small intestinal organoid (hSIO) culturing, constitutively generating all differentiated cell types while maintaining an active stem cell compartment. IL-22 does not promote the expansion of stem cells but rather slows the growth of hSIOs. In hSIOs, IL-22 is required for formation of Paneth cells, the prime producers of intestinal antimicrobial peptides (AMPs). Introduction of inflammatory bowel disease (IBD)-associated loss-of-function mutations in the IL-22 co-receptor gene IL10RB resulted in abolishment of Paneth cells in hSIOs. Moreover, IL-22 induced expression of host defense genes (such as REG1A, REG1B, and DMBT1) in enterocytes, goblet cells, Paneth cells, Tuft cells, and even stem cells. Thus, IL-22 does not directly control the regenerative capacity of crypt stem cells but rather boosts Paneth cell numbers, as well as the expression of AMPs in all cell types.
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| , , , , , , , , , | |
| Elsevier/ Cell Press | |
| The Netherlands Organisation for Scientific Research (NWO) , European Union Horizon 2020 | |
| doi.org/10.1016/j.stem.2022.08.002 | |
| Cell Stem Cell | |
| Organisation | Quantitative Developmental Biology |
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He, G.-W., Lin, L., DeMartino, J., Zheng, X., Staliarova, N., Dayton, T., … Clevers, H. (2022). Optimized human intestinal organoid model reveals interleukin-22-dependency of paneth cell formation. Cell Stem Cell, 29(9), 1333–1345.e6. doi:10.1016/j.stem.2022.08.002 |
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