Mrgprb2-dependent Mast Cell Activation Plays a Crucial Role in Acute Colitis

被引:3
|
作者
Van Remoortel, Samuel [1 ,2 ]
Lambeets, Lana [1 ,2 ]
De Winter, Benedicte [3 ,4 ]
Dong, Xinzhong [5 ]
Ruiz, Juan Pablo Rodriguez [6 ,7 ]
Kumar-Singh, Samir [1 ,2 ,6 ,7 ]
Martinez, Sales Ibiza [1 ,2 ]
Timmermans, Jean-Pierre [1 ,2 ]
机构
[1] Univ Antwerp, Lab Cell Biol & Histol, B-2610 Antwerp, Belgium
[2] Univ Antwerp, mNEURO Ctr Excellence, Antwerp, Belgium
[3] Univ Antwerp, Lab Expt Med & Pediat, Antwerp, Belgium
[4] Univ Antwerp, Infla Med Ctr Excellence, Antwerp, Belgium
[5] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD USA
[6] Univ Antwerp, Lab Med Microbiol, Antwerp, Belgium
[7] VAXINFECTIO Ctr Excellence, Antwerp, Belgium
来源
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY | 2024年 / 18卷 / 05期
关键词
Colitis; IgE-independent; Mas-related G Protein Coupled Receptor; Mast Cell; ULCERATIVE-COLITIS; AGGRAVATION; MICROBIOTA; FIBROSIS;
D O I
10.1016/j.jcmgh.2024.101391
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
BACKGROUND & AIMS: Mast cells (MCs) are typically found at mucosal surfaces, where their immunoglobulin E (IgE)-dependent activation plays a central role in allergic diseases. Over the past years, signaling through Mas-related G protein-coupled receptor b2 (Mrgprb2) in mice and MRGPRX2 in humans has gained a lot of interest as an alternative MC activation pathway with high therapeutic potential. The aim of this study was to explore the relevance of such IgE-independent, Mrgprb2mediated signaling in colonic MCs in the healthy and acutely inflamed flamed mouse colon. METHODS: Mrgprb2 expression and functionality was studied using a genetic labeling strategy combined with advancedmicroscopic imaging. Furthermore, Mrgprb2 knockout (Mrgprb2[sup]-/-[/sup]) mice were used to determine the role of this pathway in a preclinical dextran sodium sulphate (DSS) colitis model. RESULTS: We found that Mrgprb2 acts as a novel MC degranulation pathway in a large subset of connective tissue MCs in the mouse distal colon. Acute DSS colitis induced a pronounced increase of Mrgprb2-expressing MCs, which were found in close association with Substance P-positive nerve fibers. Loss of Mrgprb2-mediated signaling impaired DSSinduced neutrophil influx and significantly impacted on acute colitis progression. CONCLUSIONS: Our findings uncover a novel, IgE-independent MC degranulation pathway in the mouse colon that plays a central role in acute colitis pathophysiology, mainly by safeguarding acute colitis progression and severity in mice. This pseudo allergic, Mrgprb2-induced signaling is part of a hitherto unconsidered colonic neuro-immune pathway and might have significant potential for the further development of effective therapeutic treatment strategies for gastrointestinal disorders, such as ulcerative colitis.
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页数:19
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