髓细胞特异性缺失PDGFR-α促进肠道菌群失调,从而增加结肠炎易感性。

IF 8.3 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Journal of Crohns & Colitis Pub Date : 2023-11-24 DOI:10.1093/ecco-jcc/jjad103
Ronja Dörk, Penelope Pelczar, Ahmad M Shiri, Annika Volmari, Elisabeth Zierz, Anastasios Giannou, Marius Böttcher, Lidia Bosurgi, Samuel Huber, Carolin F Manthey
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引用次数: 0

摘要

背景与目的:炎症性肠病(IBD)的发病率正在稳步上升,因此寻找新的靶点来改善治疗是一个主要目标。PDGF家族生长因子及其受体在肠道发育早期表达,存在于成人组织的单核细胞和巨噬细胞中。巨噬细胞在IBD的发病机制中起着独特的作用,因为它们的功能对维持耐受性至关重要。方法:我们旨在研究PDGFR-α在小鼠IBD和感染性模型中骨髓表达介导肠道稳态的作用。结果:我们的研究结果表明,髓系PDGFR-α的缺失增加了对葡聚糖硫酸盐诱导的结肠炎的易感性。因此,与对照组小鼠相比,LysM-PDGFR-α-/-小鼠表现出更高的结肠炎评分,抗炎巨噬细胞水平降低。这种效应是通过促结肠炎微生物群介导的,在缺乏髓系PDGFR-α的情况下,促结肠炎微生物群发展,与对照组相比,粪菌群移植后,无菌小鼠结肠炎易感性增加。此外,LysM-PDGFR-α-/-小鼠有漏肠,并伴有吞噬功能受损,导致严重的屏障缺陷。结论:综上所述,我们的研究结果表明髓系PDGFR-α通过促进保护性肠道微生物群和提供抗炎巨噬细胞表型,在维持肠道稳态中起保护作用。
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Myeloid Cell-Specific Deletion of PDGFR-α Promotes Dysbiotic Intestinal Microbiota and thus Increased Colitis Susceptibility.

Background and aims: The incidence of inflammatory bowel diseases [IBD] is steadily increasing, and thus the identification of new targets to improve therapy is a major goal. Growth factors of the PDGF family and their receptors are expressed early in intestinal development and are found in mononuclear cells and macrophages in adult tissues. Macrophages play a distinct role in the pathogenesis of IBD since their function is crucial to maintaining tolerance.

Methods: We aimed to study the role of myeloid expression of PDGFR-α in mediating intestinal homeostasis in mouse IBD and infectious models.

Results: Our results show that loss of myeloid PDGFR-α increases susceptibility to dextran saline sulphate-induced colitis. Accordingly, LysM-PDGFR-α-/- mice showed higher colitis scores, and reduced levels of anti-inflammatory macrophages compared to control mice. This effect was mediated via a pro-colitogenic microbiota, which developed in the absence of myeloid PDGFR-α and caused increased colitis susceptibility in gnotobiotic mice upon faecal microbiota transplantation compared to controls. Furthermore, LysM-PDGFR-α-/- mice had a leaky gut, accompanied by impaired phagocytosis, resulting in a severe barrier defect.

Conclusions: Taken together, our results indicate a protective role for myeloid PDGFR-α in maintaining gut homeostasis by promoting a protective intestinal microbiota and providing an anti-inflammatory macrophage phenotype.

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来源期刊
Journal of Crohns & Colitis
Journal of Crohns & Colitis 医学-胃肠肝病学
CiteScore
15.50
自引率
7.50%
发文量
1048
审稿时长
1 months
期刊介绍: Journal of Crohns and Colitis is concerned with the dissemination of knowledge on clinical, basic science and innovative methods related to inflammatory bowel diseases. The journal publishes original articles, review papers, editorials, leading articles, viewpoints, case reports, innovative methods and letters to the editor.
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