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.
引用
收藏
页数:19
相关论文
共 50 条
  • [41] TNF plays a crucial role in inflammation by signaling via T cell TNFR2
    Alam, Muhammad S.
    JOURNAL OF IMMUNOLOGY, 2021, 206
  • [42] The crucial role that hippocampus Cyclooxygenase-2 plays in memory
    Ni, Hong
    Guo, Zhongzhao
    Wu, Yue
    Wang, Jie
    Yang, Yang
    Zhu, Zilu
    Wang, Deheng
    EUROPEAN JOURNAL OF NEUROSCIENCE, 2023, 58 (10) : 4123 - 4136
  • [43] Role of serine esterases in mast cell activation
    Khiav, BE
    Pearce, FL
    BRITISH JOURNAL OF PHARMACOLOGY, 1998, 123 (06) : 1267 - 1273
  • [44] New insight into prurigo nodularis: Proadrenomedullin N-terminal 20 peptide mediates mouse mast cell activation via Mrgprb2
    Shao, Yixin
    Xiao, Zijing
    Jin, Yinghong
    Zhu, Yiqi
    Shen, Yanyun
    Jin, Taiyu
    Tang, Hui
    Wang, Duoqin
    SKIN RESEARCH AND TECHNOLOGY, 2024, 30 (02)
  • [45] Mast cell activation induced by tamoxifen citrate via MRGPRX2 plays a potential adverse role in breast cancer treatment
    Gao, Jiapan
    Su, Xinyue
    Zhang, Yuxiu
    Ma, Xiaoyu
    Ren, Bingxi
    Lei, Panpan
    Jin, Jiming
    Ma, Weina
    BIOCHEMICAL PHARMACOLOGY, 2025, 233
  • [46] The membrane proximal region of FcεRIα -: Plays a unique role in receptor signaling and mast cell/basophil activation
    Kricek, F
    Nechansky, A
    Ruf, C
    Effenberger, F
    Stumper, B
    Mayer, P
    de Vries, J
    Robertson, MW
    ALLERGY FRONTIERS AND FUTURES, 2003, : 182 - 188
  • [47] Parkin plays a crucial role in acute viral myocarditis by regulating mitophagy activity
    Qiu, Yixuan
    Xu, Jing
    Chen, Yilian
    Wu, Yihao
    Lin, Yuan-nan
    Liu, Weike
    Wang, Zhening
    Wu, Yuqing
    Qian, Xinge
    Li, Yue-Chun
    THERANOSTICS, 2024, 14 (13): : 5303 - 5315
  • [48] On the regulation of IgE-dependent mast cell activation
    Uermoesi, C.
    Manolova, V
    Beerli, R.
    Bauer, M.
    Bachmann, M. F.
    SWISS MEDICAL WEEKLY, 2009, 139 (9-10) : 10S - 10S
  • [49] Proline 36 of the Factor XIII Activation Peptide Plays a Crucial Role in Substrate Recognition and Zymogen Activation
    Li, Bojun
    Billur, Ramya
    Maurer, Muriel C.
    Kohler, Hans P.
    Mueller, Pascale Raddatz
    Alberio, Lorenzo
    Schroeder, Verena
    THROMBOSIS AND HAEMOSTASIS, 2018, 118 (12) : 2037 - 2045
  • [50] The mast cell plays a central role in the immune system of teleost fish
    Sfacteria, Alessandra
    Brines, Michael
    Blank, Ulrich
    MOLECULAR IMMUNOLOGY, 2015, 63 (01) : 3 - 8