Optimized human intestinal organoid model reveals interleukin-22-dependency of paneth cell formation.
IL-22
IL10RB
Paneth cells
anti-microbial proteins
enterocytes
inflammatory bowel disease
intestinal stem cells
mTOR
organoids
regeneration
Journal
Cell stem cell
ISSN: 1875-9777
Titre abrégé: Cell Stem Cell
Pays: United States
ID NLM: 101311472
Informations de publication
Date de publication:
01 09 2022
01 09 2022
Historique:
received:
11
02
2022
revised:
01
07
2022
accepted:
05
08
2022
pubmed:
25
8
2022
medline:
9
9
2022
entrez:
24
8
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 36002022
pii: S1934-5909(22)00338-1
doi: 10.1016/j.stem.2022.08.002
pmc: PMC9438971
pii:
doi:
Substances chimiques
Calcium-Binding Proteins
0
DMBT1 protein, human
0
DNA-Binding Proteins
0
Interleukins
0
Tumor Suppressor Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1333-1345.e6Commentaires et corrections
Type : ErratumIn
Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests H.C. is an inventor of several patents related to organoid technology; his full disclosure is given at https://www.uu.nl/staff/JCClevers/.
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