小柯机器人

荷兰马克西玛公主儿科肿瘤中心Hans Clevers团队近期取得重要工作进展，他们研究利用优化的人类肠道类器官模型揭示了潘氏细胞的形成对白细胞介素-22的依赖性。该项研究成果2022年8月23日在线发表于《细胞—干细胞》杂志上。

研究人员优化了人类小肠类器官（hSIO）培养，组成性地产生所有分化的细胞类型，同时保持活跃的干细胞区室。IL-22不促进干细胞的扩增，而是减缓hSIO的生长。 在hSIOs中，IL-22是潘氏细胞的形成所必需的，潘氏细胞是肠道抗菌肽（AMP）的主要生产者。在IL-22共受体基因IL10RB中引入与炎症性肠病（IBD）相关的功能丧失突变导致hSIO中的潘氏细胞消失。

 此外，IL-22在肠细胞、杯状细胞、潘氏细胞、Tuft细胞甚至干细胞中诱导宿主防御基因（如 REG1A、REG1B 和 DMBT1）的表达。 因此，IL-22不直接控制隐窝干细胞的再生能力，而是增加潘氏细胞数量，以及所有细胞类型中AMP的表达。

据介绍，IL-22在肠道病理生理学中的相反作用已经被提出。

附：英文原文

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

Author: Gui-Wei He, Lin Lin, Jeff DeMartino, Xuan Zheng, Nadzeya Staliarova, Talya Dayton, Harry Begthel, Willine J. van de Wetering, Eduard Bodewes, Jeroen van Zon, Sander Tans, Carmen Lopez-Iglesias, Peter J. Peters, Wei Wu, Daniel Kotlarz, Christoph Klein, Thanasis Margaritis, Frank Holstege, Hans Clevers

Issue&Volume: 2022-08-23

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.

DOI: 10.1016/j.stem.2022.08.002

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(22)00338-1

Cell Stem Cell：《细胞—干细胞》，创刊于2007年。隶属于细胞出版社，最新IF：25.269
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