TY - JOUR
KW - Calcium-Binding Proteins
KW - DNA-Binding Proteins
KW - Humans
KW - IL-22
KW - IL10RB
KW - Interleukins
KW - Intestinal Mucosa
KW - Intestine, Small
KW - organoids
KW - Paneth Cells
KW - Paneth Cells
KW - Tumor Suppressor Proteins
KW - anti-microbial proteins
KW - enterocytes
KW - inflammatory bowel disease
KW - intestinal stem cells
KW - mTOR
KW - organoids
KW - Regeneration
AU - Gui-Wei He
AU - Lin Lin
AU - Jeff DeMartino
AU - Xuan Zheng
AU - Nadzeya Staliarova
AU - Talya Dayton
AU - Harry Begthel
AU - Willine J. van de Wetering
AU - Eduard Bodewes
AU - Jeroen van Zon
AU - Sander Tans
AU - Carmen Lopez-Iglesias
AU - Peter J. Peters
AU - Wei Wu
AU - Daniel Kotlarz
AU - Christoph Klein
AU - Thanasis Margaritis
AU - Frank Holstege
AU - Hans Clevers
AB - 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.
BT - Cell Stem Cell
DA - 2022-09-01
DO - 10.1016/j.stem.2022.08.002
IS - 9
LA - eng
N2 - 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.
PY - 2022
SP - 1333
EP - 1345.e6
T2 - Cell Stem Cell
TI - Optimized human intestinal organoid model reveals interleukin-22-dependency of paneth cell formation
VL - 29
SN - 1875-9777
ER -