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
{"title":"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。","authors":"Ronja Dörk, Penelope Pelczar, Ahmad M Shiri, Annika Volmari, Elisabeth Zierz, Anastasios Giannou, Marius Böttcher, Lidia Bosurgi, Samuel Huber, Carolin F Manthey","doi":"10.1093/ecco-jcc/jjad103","DOIUrl":null,"url":null,"abstract":"<p><strong>Background and aims: </strong>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.</p><p><strong>Methods: </strong>We aimed to study the role of myeloid expression of PDGFR-α in mediating intestinal homeostasis in mouse IBD and infectious models.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":15547,"journal":{"name":"Journal of Crohns & Colitis","volume":null,"pages":null},"PeriodicalIF":8.3000,"publicationDate":"2023-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Myeloid Cell-Specific Deletion of PDGFR-α Promotes Dysbiotic Intestinal Microbiota and thus Increased Colitis Susceptibility.\",\"authors\":\"Ronja Dörk, Penelope Pelczar, Ahmad M Shiri, Annika Volmari, Elisabeth Zierz, Anastasios Giannou, Marius Böttcher, Lidia Bosurgi, Samuel Huber, Carolin F Manthey\",\"doi\":\"10.1093/ecco-jcc/jjad103\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background and aims: </strong>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.</p><p><strong>Methods: </strong>We aimed to study the role of myeloid expression of PDGFR-α in mediating intestinal homeostasis in mouse IBD and infectious models.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>\",\"PeriodicalId\":15547,\"journal\":{\"name\":\"Journal of Crohns & Colitis\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":8.3000,\"publicationDate\":\"2023-11-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Crohns & Colitis\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1093/ecco-jcc/jjad103\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Crohns & Colitis","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/ecco-jcc/jjad103","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
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。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
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.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
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.
期刊最新文献
Peripheral Blood DNA Methylation Signatures and Response to Tofacitinib in Moderate-to-severe Ulcerative Colitis. Whole Blood DNA Methylation Changes Are Associated with Anti-TNF Drug Concentration in Patients with Crohn's Disease. 6-Mercaptopurine in ulcerative colitis: the potential of upfront dosing with allopurinol. Mitigating the Risk of Tofacitinib-induced Adverse Events in the Elderly Population with Ulcerative Colitis. Temporary Faecal Diversion for Refractory Perianal and/or Distal Colonic Crohn's Disease in the Biologic Era: An Updated Systematic Review with Meta-analysis.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1