潘尼斯电池
生物
类有机物
地穴
细胞生物学
干细胞
细胞分化
细胞
肠上皮
免疫学
上皮
基因
小肠
遗传学
内分泌学
作者
Gui-Wei He,Lin Lin,Jeff DeMartino,Xuan Zheng,Nadzeya Staliarova,Talya L. Dayton,Harry Begthel,Willine J. van de Wetering,Eduard Bodewes,Jeroen S. van Zon,Sander J. Tans,Carmen López‐Iglesias,Peter J. Peters,Wei Wu,Daniel Kotlarz,Christoph Klein,Thanasis Margaritis,Frank C. P. Holstege,Hans Clevers
出处
期刊:Cell Stem Cell
[Elsevier]
日期:2022-09-01
卷期号:29 (9): 1333-1345.e6
被引量:59
标识
DOI:10.1016/j.stem.2022.08.002
摘要
Summary
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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