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Review
. 2025 Jan 29;13(2):320.
doi: 10.3390/biomedicines13020320.

Beyond the "Master" Role in Allergy: Insights into Intestinal Mast Cell Plasticity and Gastrointestinal Diseases

Rosa Molfetta  1 , Alessia Carnevale  1 , Caterina Marangio  1 , Erisa Putro  1 , Rossella Paolini  1
Affiliations
Review

Beyond the "Master" Role in Allergy: Insights into Intestinal Mast Cell Plasticity and Gastrointestinal Diseases

Rosa Molfetta et al. Biomedicines. .

Abstract

Mast cells (MCs) are essential components of the immune system that enter the circulation as immature bone marrow progenitors and differentiate in peripheral organs under the influence of microenvironment factors. As tissue-resident secretory immune cells, MCs rapidly detect the presence of bacteria and parasites because they harbor many surface receptors, which enable their activation via a multitude of stimuli. MC activation has been traditionally linked to IgE-mediated allergic reactions, but MCs play a pivotal role in different physiological and pathological processes. In gut, MCs are essential for the maintenance of gastrointestinal (GI) barrier function, and their interactions with neurons, immune cells, and epithelial cells have been related to various GI disorders. This review recapitulates intestinal MC roles in diseases with a main focus on inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). Emerging therapies targeting MCs and their mediators in clinical practices will also be discussed.

Keywords: gut inflammation; homeostasis; intestinal mast cells.

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Conflict of interest statement

The authors declare no commercial or financial conflicts of interest.

Figures

Figure 1
Figure 1
Mast cells control gut homeostasis and inflammation. Intestinal MCs are involved in the maintenance of homeostasis (left side) as well as in orchestrating local inflammation leading to the development of IBD (right side). The main effects of mast cell mediators are depicted. Modified from Van Remoortel S et al., Cell Mol Gastroenterol Hepatol. 2024, 18, 101391 [83] and created in https://BioRender.com.
Figure 2
Figure 2
Mast cells and nerve bidirectional communication and therapeutic interventions. Neurons produce neuropeptides and hormones that trigger mast cell activation and degranulation; in turn, mast cells produce histamine, serotonin, and tryptase that can regulate neuronal function. The main inhibitors of mast cells and their mediators are illustrated. Modified from Jacobson A et al. Mucosal Immunology 2021, 14, 555–565 [111] and created in https://BioRender.com.
See this image and copyright information in PMC

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