@article{1551,
  keywords = {Calcium-Binding Proteins, DNA-Binding Proteins, Humans, IL-22, IL10RB, Interleukins, Intestinal Mucosa, Intestine, Small, organoids, Paneth Cells, Paneth Cells, Tumor Suppressor Proteins, anti-microbial proteins, enterocytes, inflammatory bowel disease, intestinal stem cells, mTOR, organoids, Regeneration},
  author = {Gui-Wei He and Lin Lin and Jeff DeMartino and Xuan Zheng and Nadzeya Staliarova and Talya Dayton and Harry Begthel and Willine J. van de Wetering and Eduard Bodewes and Jeroen van Zon and Sander Tans and Carmen Lopez-Iglesias and Peter J. Peters and Wei Wu and Daniel Kotlarz and Christoph Klein and Thanasis Margaritis and Frank Holstege and Hans Clevers},
  title = {Optimized human intestinal organoid model reveals interleukin-22-dependency of paneth cell formation},
  abstract = {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.},
  year = {2022},
  journal = {Cell Stem Cell},
  volume = {29},
  pages = {1333-1345.e6},
  month = {2022-09-01},
  issn = {1875-9777},
  doi = {10.1016/j.stem.2022.08.002},
  language = {eng},
}