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Mast Cells in Human Health and Diseases—3rd Edition
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Mast Cells in Human Health and Diseases—3rd Edition

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (30 November 2025) | Viewed by 14205

Special Issue Editor

Prof. Dr. Giovanna Traina

E-Mail Website
Guest Editor
Department of Pharmaceutical Sciences, University of Perugia, Via Romana, 06126 Perugia, Italy
Interests: Inflammation; neuroinflammation; gut-brain axis; mast cells; learning and memory
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Increasing amounts of evidence suggest that mast cells play a crucial role in human health and diseases.

Mast cells are known to be cells involved in allergic reactions through degranulation and the release of a variety of mediators with vasoactive, inflammatory, and nociceptive activities. Mast cells are sensors of the environment, able to respond promptly and selectively. Mast cells are intriguing and multifactorial cells and play a leading role in various pathological conditions.

The localization of mast cells within the tissue and their expression of specific mediators, such as chymases or tryptases, are important pieces of evidence from the diagnostic point of view. Chronic inflammation is a common mediator of various disorders which include many pathological conditions, pain, migraine, depression, anxiety, autoimmune diseases, and fibromyalgia, but also Alzheimer’s disease, multiple sclerosis, atherosclerosis, and cardiovascular diseases. The modulation of the hyperactivity of mast cells and the reduction in the release of inflammatory factors could constitute new frontiers of therapeutic interventions aimed at preventing chronic inflammation.

Topics:

  • New developments in mast cell management in human disorders;
  • New molecular insights in mast cell control;
  • Mast cells and the microbiome;
  • Mast cells and nociception;
  • Mast cells and food allergies;
  • Mast cells and neuroinflammation;
  • Mast cells and stress.

Dr. Giovanna Traina
Guest Editor

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Keywords

  • mast cells
  • human diseases
  • pain
  • cardiovascular diseases
  • microbiome
  • food allergy
  • stress
  • cancer

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Published Papers (5 papers)

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Research

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19 pages, 1902 KB  
Article
Modulation of Mast Cell Activation via MRGPRX2 by Natural Oat Extract
by Susanne Kaesler, Désirée Argiriu, Shyami M. Kandage, Karla Schönfeldt, Shalva Lekiashvili, Ceren N. Dengiz, Neslim Ercan, Caterina Iuliano, Martina Herrmann, Maria Reichenbach, Dominik Cichowski, Magda Babina, Miriam Hils, Martin Köberle and Tilo Biedermann
Int. J. Mol. Sci. 2026, 27(1), 334; https://doi.org/10.3390/ijms27010334 - 28 Dec 2025
Viewed by 1672
Abstract
The Mas-related G protein-coupled receptor (MRGPR) X2 is expressed on skin mast cells and can be stimulated by an unusually broad spectrum of ligands, including specific drugs and even endogenous peptides. MRGPRX2 activation can induce mast cell degranulation and consequently mediator release, leading [...] Read more.
The Mas-related G protein-coupled receptor (MRGPR) X2 is expressed on skin mast cells and can be stimulated by an unusually broad spectrum of ligands, including specific drugs and even endogenous peptides. MRGPRX2 activation can induce mast cell degranulation and consequently mediator release, leading to inflammatory and hypersensitivity reactions. In addition, MRGPRX2 mediates pain and itching sensations, leading to increased efforts to identify MRGPRX2 inhibitors, including plant-derived compounds. Components within oat extracts have been shown to mediate anti-inflammatory and itch-relieving properties, but a possible inhibitory effect on MRGPRX2 activation has not yet been investigated. We aimed to fill this gap and explored whether an oat kernel extract can modulate MRGPRX2 activation. For this purpose, we established a mast cell model with the human LAD2 cell line and used it to investigate the consequences of exposure to oat extract. While we did not observe any influence on cell viability, we analyzed the impact of oat extract on MRGPRX2-mediated mast cell activation and degranulation initiated by the three confirmed MRGPRX2 ligands c48/80, substance P, and cortistatin 14. Exposure to oat extract resulted in a significant reduction in mast cell degranulation for all three ligands, as assessed by the release of β-hexosaminidase, tryptase, cell surface expression of CD63 and CD107a, and phosphorylation of ERK. All results were confirmed with primary human mast cells. Thus, we demonstrated for the first time that oat extract leads to a significant reduction in MRGPRX2 activation, pointing to a previously unrecognized capacity of natural compounds to modulate this pathway. Full article
(This article belongs to the Special Issue Mast Cells in Human Health and Diseases—3rd Edition)
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18 pages, 1944 KB  
Article
Introduction of Mature Mast Cells into Bone Marrow Alters Bone Metabolism in Growing Mice
by Carmen P. Wong, Jessica A. Keune, Kenneth A. Philbrick, Adam J. Branscum, Urszula T. Iwaniec and Russell T. Turner
Int. J. Mol. Sci. 2025, 26(24), 11952; https://doi.org/10.3390/ijms262411952 - 11 Dec 2025
Viewed by 800
Abstract
There is evidence that mast cells contribute to skeletal response to injury, but it is less clear whether these immune cells directly influence normal bone growth and turnover. Mature mast cells are common in the bone marrow of humans and rats, but have [...] Read more.
There is evidence that mast cells contribute to skeletal response to injury, but it is less clear whether these immune cells directly influence normal bone growth and turnover. Mature mast cells are common in the bone marrow of humans and rats, but have not been convincingly demonstrated to be present in the bone marrow of healthy mice, potentially limiting the mouse as a model for characterizing the full range of mast cell/bone cell interactions. An initial goal of this investigation was to comprehensively screen seven strains of mice for mature mast cells in bone marrow. Finding none, we then investigated three approaches to home these cells to the marrow of mice unable to generate mast cells: (1) administration of soluble kit ligand to membrane kit ligand-deficient KitSl/Sld mice, (2) adoptive transfer of wild-type hematopoietic stem cells to kit receptor-deficient KitW/W−v mice, and (3) adoptive transfer of wild-type mouse bone marrow-derived mast cells generated in vitro and delivered intravenously to KitW/W-v mice. Only the third approach was successful. Using this method, we then evaluated the impact of bone marrow-derived mast cells on bone mass, architecture, turnover, and gene expression. The adoptive transfer of mast cells resulted in alterations in cancellous bone microarchitecture and cell populations in the vertebra, and in differential expression of genes associated with bone metabolism in the tibia. Taken together, our results support the concept that bone marrow mast cells influence bone metabolism and suggest that homing mast cells to the bone marrow of mice is a useful model to understand the role of these cells in skeletal health and disease. Full article
(This article belongs to the Special Issue Mast Cells in Human Health and Diseases—3rd Edition)
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19 pages, 4942 KB  
Article
The Therapeutic Potential of Kiwi Extract as a Source of Cysteine Protease Inhibitors on DNCB-Induced Atopic Dermatitis in Mice and Human Keratinocyte HaCaT Cells
by Hye Ryeon Yang, Most Nusrat Zahan, Du Hyeon Hwang, Ramachandran Loganathan Mohan Prakash, Deva Asirvatham Ravi, Il-Hwa Hong, Woo Hyun Kim, Jong-Hyun Kim, Euikyung Kim and Changkeun Kang
Int. J. Mol. Sci. 2025, 26(4), 1534; https://doi.org/10.3390/ijms26041534 - 12 Feb 2025
Cited by 1 | Viewed by 2683
Abstract
The discovery of effective cysteine protease inhibitors with crude protein kiwi extracts (CPKEs) has created novel challenges and prospects for pharmaceutical development. Despite extensive research on CPKEs, limited research has been conducted on treating atopic dermatitis (AD). Therefore, the objective of this work [...] Read more.
The discovery of effective cysteine protease inhibitors with crude protein kiwi extracts (CPKEs) has created novel challenges and prospects for pharmaceutical development. Despite extensive research on CPKEs, limited research has been conducted on treating atopic dermatitis (AD). Therefore, the objective of this work was to investigate the anti-inflammatory effects of CPKEs on TNF-α activation in a HaCaT cell model and in a DNCB (1-chloro-2, 4-dinitrochlorobenzene)-induced atopic dermatitis animal model. The molecular weight of the CPKE was determined using SDS-PAGE under non-reducing (17 kDa and 22 kDa) and reducing conditions (25 kDa, 22 kDa, and 15 kDa), whereas gelatin zymography was performed to examine the CPKE’s inhibitory impact on cysteine protease (actinidin and papain) activity. Moreover, the CPKE remains stable at 60 °C, with pH levels varying from 4 to 11, as determined by the azocasein assay. CPKE treatment decreased the phosphorylation of mitogen-activated protein kinase (MAPK) and Akt, along with the activation of nuclear factor-kappa B (NF-κB)-p65 in tumor necrosis factor-α (TNF-α)-stimulated HaCaT cells. Five-week-old BALB/c mice were treated with DNCB to act as an AD-like animal model. The topical application of CPKE to DNCB-treated mice for three weeks substantially decreased clinical dermatitis severity and epidermal thickness and reduced eosinophil infiltration and mast cells into ear and skin tissues. These findings imply that CPKE derived from kiwifruit might be a promising therapy option for inflammatory skin diseases such as AD. Full article
(This article belongs to the Special Issue Mast Cells in Human Health and Diseases—3rd Edition)
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Review

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18 pages, 556 KB  
Review
Role of Mast Cells and Their Mediators in Chronic Kidney Diseases
by Maria Tziastoudi, Christos Cholevas, Theodoros Eleftheriadis, Ioannis Stefanidis and Theoharis C. Theoharides
Int. J. Mol. Sci. 2025, 26(20), 9981; https://doi.org/10.3390/ijms26209981 - 14 Oct 2025
Viewed by 2468
Abstract
Chronic kidney disease (CKD) affects as many as 10% of the population, which translates to about 850 million globally. Even though genetics, diabetes, and hypertension contribute to CKD, the underlying pathologic processes remain poorly understood. Mast cells (MCs) are unique tissue immune cells [...] Read more.
Chronic kidney disease (CKD) affects as many as 10% of the population, which translates to about 850 million globally. Even though genetics, diabetes, and hypertension contribute to CKD, the underlying pathologic processes remain poorly understood. Mast cells (MCs) are unique tissue immune cells capable of secreting numerous biologically active molecules. MCs have been associated with kidney diseases and poor CKD outcomes, but they have received limited attention in CKD research. MCs are typically located perivascularly and are identified through kidney biopsies, which limits their diagnostic utility. MC-specific biomarkers such as histamine and the proteases chymase and tryptase show potential, but signature biomarker profiles are needed. While MC biomarkers have been studied in non-renal diseases, their clinical relevance in kidney disease remains underexplored. This review aims to clarify the role of MCs in kidney diseases, such as diabetic nephropathy, IgA nephropathy, hypertensive nephropathy, pruritus, parathyroidism, renal amyloidosis, and lupus nephritis, as well as in conditions such as kidney fibrosis, inflammation, and kidney transplant rejection. Evidence indicates an increased number of MCs, as judged by increased urine levels of histamine, chymase, IL-33, metalloproteinase-9 (MMP-9), and tryptase. In conclusion, MCs are involved in the pathogenesis of CKD and may represent new targets for early diagnosis, prevention, and treatment. Full article
(This article belongs to the Special Issue Mast Cells in Human Health and Diseases—3rd Edition)
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32 pages, 1208 KB  
Review
Role of Mast Cells in Human Health and Disease: Controversies and Novel Therapies
by Miguel Ángel Galván-Morales, Juan Carlos Vizuet-de-Rueda, Josaphat Miguel Montero-Vargas and Luis M. Teran
Int. J. Mol. Sci. 2025, 26(18), 8895; https://doi.org/10.3390/ijms26188895 - 12 Sep 2025
Cited by 7 | Viewed by 5629
Abstract
Mast cells have been implicated in allergic diseases such as asthma, rhinitis, conjunctivitis, atopic dermatitis, urticaria, and anaphylaxis. However, it is now well established that they also fulfill critical roles in tissue homeostasis, repair, and defense. Despite considerable progress, their ontogeny, proliferation, and [...] Read more.
Mast cells have been implicated in allergic diseases such as asthma, rhinitis, conjunctivitis, atopic dermatitis, urticaria, and anaphylaxis. However, it is now well established that they also fulfill critical roles in tissue homeostasis, repair, and defense. Despite considerable progress, their ontogeny, proliferation, and differentiation remain subjects of debate, as does their involvement in a wide spectrum of diseases, including cancer and cardiovascular disorders. What remains indisputable is their essential contribution to both innate and adaptive immune responses. Importantly, the activity of their effector molecules can elicit either protective or deleterious outcomes. A complete absence of mast cells (MCs) in humans would undoubtedly provide valuable insight into their fundamental role in immunity, much as neutropenia and agranulocytosis have historically clarified the functions of neutrophils. In this review, we provide a comprehensive overview of mast cell (MC) biology, emphasizing their functional diversity and pathogenic potential. Furthermore, we highlight emerging therapeutic strategies, particularly the use of inhibitors and monoclonal antibodies, which are reshaping current approaches to conditions such as allergy, mastocytosis, and related disorders. Full article
(This article belongs to the Special Issue Mast Cells in Human Health and Diseases—3rd Edition)
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