Optimized human intestinal organoid model reveals interleukin-22-dependency of paneth cell formation

He, Gui-Wei; Lin, Lin; DeMartino, Jeff; Zheng, Xuan; Staliarova, Nadzeya; Dayton, Talya; Begthel, Harry; Wetering, Willine J. van de; Bodewes, Eduard; Zon, Jeroen van; Tans, Sander; Lopez-Iglesias, Carmen; Peters, Peter J.; Wu, Wei; Kotlarz, Daniel; Klein, Christoph; Margaritis, Thanasis; Holstege, Frank und Clevers, Hans (2022): Optimized human intestinal organoid model reveals interleukin-22-dependency of paneth cell formation. In: Cell Stem Cell, Bd. 29, Nr. 9: S. 1333-1345

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 ca-pacity of crypt stem cells but rather boosts Paneth cell numbers, as well as the expression of AMPs in all cell types.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1934-5909
• Sprache: Englisch