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基质细胞亚群在实验性结肠炎中表现出模型依赖性变化,并影响上皮组织修复和免疫细胞激活。

Stromal Cell Subsets Show Model-Dependent Changes in Experimental Colitis and Affect Epithelial Tissue Repair and Immune Cell Activation.

作者信息

Zhou Zhou, Su Jie, van Os Bram W, Plug Leonie G, de Jonge-Muller Eveline S M, Brands Lei, Janson Stef G T, van de Beek Lydia M, van der Meulen-de Jong Andrea E, Hawinkels Lukas J A C, Barnhoorn Marieke C

机构信息

Department of Gastroenterology and Hepatology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.

出版信息

Inflamm Bowel Dis. 2025 Apr 10;31(4):1051-1066. doi: 10.1093/ibd/izae255.

Abstract

BACKGROUND

Previous work on inflammatory bowel disease (IBD) revealed changes in the abundance of colonic stromal subsets during intestinal inflammation. However, it is currently unknown whether these stromal cell subset changes are also reflected in different IBD mouse models and how commonly used IBD therapies affect stromal cell subset composition.

METHODS

Stromal subset markers CD55, C-X-C motif chemokine 12 (CXCL12), podoplanin (PDPN), CD90, and CD73 were analyzed by flow cytometry in 3 mouse models for IBD, namely interleukin (IL)-10 knockout (KO), dextran sulfate sodium-induced, and T-cell transfer model for colitis. Next, the effects of IBD therapies on the stromal subset composition were studied. In vitro experiments were performed to study the interaction between stromal cell subsets and epithelial/immune cells.

RESULTS

The colitis-induced changes in the abundance of stromal cell subsets differed considerably between the 3 colitis mouse models. Interestingly, treatment with IBD medication affected specific stromal subsets in a therapy and model-specific manner. In vitro experiments showed that specific stromal subsets affected epithelial wound healing and/or T-cell activation.

CONCLUSIONS

The relative abundance changes of stromal cell subsets during experimental colitis differ between 3 established colitis models. Treatment with IBD therapies influences stromal subset abundance, indicating their importance in IBD pathogenesis, possibly through affecting epithelial migration, and T-cell activation.

摘要

背景

先前关于炎症性肠病(IBD)的研究揭示了肠道炎症期间结肠基质亚群丰度的变化。然而,目前尚不清楚这些基质细胞亚群的变化是否也反映在不同的IBD小鼠模型中,以及常用的IBD疗法如何影响基质细胞亚群的组成。

方法

通过流式细胞术分析了3种IBD小鼠模型(即白细胞介素(IL)-10基因敲除(KO)、葡聚糖硫酸钠诱导的结肠炎模型和结肠炎T细胞转移模型)中的基质亚群标志物CD55、C-X-C基序趋化因子12(CXCL12)、血小板内皮细胞黏附分子(PDPN)、CD90和CD73。接下来,研究了IBD疗法对基质亚群组成的影响。进行了体外实验以研究基质细胞亚群与上皮/免疫细胞之间的相互作用。

结果

3种结肠炎小鼠模型中,结肠炎诱导的基质细胞亚群丰度变化差异很大。有趣的是,IBD药物治疗以治疗方法和模型特异性的方式影响特定的基质亚群。体外实验表明,特定的基质亚群影响上皮伤口愈合和/或T细胞活化。

结论

在3种已建立的结肠炎模型中,实验性结肠炎期间基质细胞亚群的相对丰度变化有所不同。IBD疗法治疗会影响基质亚群的丰度,表明它们在IBD发病机制中具有重要作用,可能是通过影响上皮迁移和T细胞活化来实现的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/358a/11985400/58540390ddbb/izae255_fig1.jpg

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