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Cells
Special Issues
New Insights into Mast Cells Biology
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New Insights into Mast Cells Biology

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 20138

Special Issue Editors

Dr. Katarina Stevanovic

E-Mail Website
Guest Editor
1. Institute of Allergology, Charité—Universitätsmedizin Berlin, 10117 Berlin, Germany
2. Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Allergology and Immunology, 12203 Berlin, Germany
Interests: allergy; pseudo-allergy; food allergy; allergy-friendly environment; mast cells; MRGPRX2
Prof. Dr. Torsten Zuberbier

E-Mail Website
Guest Editor
1. Institute of Allergology, Charité—Universitätsmedizin Berlin, 10117 Berlin, Germany
2. Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Allergology and Immunology, 12203 Berlin, Germany
Interests: skin; allergy; pseudo-allergy; food allergy; atopic dermatitis; urticaria mast cells; MRGPRX2

Special Issue Information

Dear Colleagues,

Mast cells (MCs) are crucial effector cells in type I allergic reactions. Until recently, IgE was the best-known mechanism to trigger their degranulation and release of a vast array of allergic mediators. However, there are many more pathways for eliciting mast cell responses and there are many other mediators. Histamine is the most abundant mediator that is released; however, other cytokines can be of great immunological importance. Based on our current knowledge, one of the most important mast cell receptors is the recently uncovered Mas-related G protein-coupled receptor type 2 (MRGPRX2).

In this Special Issue of Cells entitled New Insights into Mast Cells Biology, we are inviting contributions in the form of original research articles, reviews, or shorter perspective articles on all aspects related to, but not limited to, the topics of mast cells development, IgE- and non-IgE-mediated MC activation, particularly via the MRGPRX2 receptor, the role of autoimmune reactions in mast cell-dependent diseases such as urticaria, and drugs that target mast cell survival and their potential adverse events.

Dr. Katarina Stevanovic
Prof. Dr. Torsten Zuberbier
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • allergy
  • pseudoallergy
  • autoimmune diseases
  • mast cell development
  • MRGPRX
  • IgE
  • mast cell activation
  • mast cell cytokines

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Published Papers (5 papers)

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Research

Jump to: Review, Other

21 pages, 4202 KiB  
Article
Synergism between IL-33 and MRGPRX2/FcεRI Is Primarily Due to the Complementation of Signaling Modules, and Only Modestly Supplemented by Prolonged Activation of Selected Kinases
by Kristin Franke, Zhuoran Li, Gürkan Bal, Torsten Zuberbier and Magda Babina
Cells 2023, 12(23), 2700; https://doi.org/10.3390/cells12232700 - 24 Nov 2023
Cited by 1 | Viewed by 1763
Abstract
Skin mast cells (MCs) express high levels of MRGPRX2, FcεRI, and ST2, and vigorously respond to their ligands when triggered individually. IL-33/ST2 also potently synergizes with other receptors, but the molecular underpinnings are poorly understood. Human skin-derived MCs were stimulated via different receptors [...] Read more.
Skin mast cells (MCs) express high levels of MRGPRX2, FcεRI, and ST2, and vigorously respond to their ligands when triggered individually. IL-33/ST2 also potently synergizes with other receptors, but the molecular underpinnings are poorly understood. Human skin-derived MCs were stimulated via different receptors individually or jointly in the presence/absence of selective inhibitors. TNF was quantified by ELISA. Signaling cascades were studied by immunoblot. TNF was stimulated by FcεRI ≈ ST2 > MRGPRX2. Surprisingly, neither FcεRI nor MRGPRX2 stimulation elicited NF-κB activation (IκB degradation, p65 phosphorylation) in stark contrast to IL-33. Accordingly, TNF production did not depend on NF-κB in FcεRI- or MRGPRX2-stimulated MCs, but did well so downstream of ST2. Conversely, ERK1/2 and PI3K were the crucial modules upon FcεRI/MRGPRX2 stimulation, while p38 was key to the IL-33-elicited route. The different signaling prerequisites were mirrored by their activation patterns with potent pERK/pAKT after FcεRI/MRGPRX2, but preferential induction of pp38/NF-κB downstream of ST2. FcεRI/MRGPRX2 strongly synergized with IL-33, and some synergy was still observed upon inhibition of each module (ERK1/2, JNK, p38, PI3K, NF-κB). IL-33’s contribution to synergism was owed to p38 > JNK > NF-κB, while the partner receptor contributed through ERK > PI3K ≈ JNK. Concurrent IL-33 led to slightly prolonged pERK (downstream of MRGPRX2) or pAKT (activated by FcεRI), while the IL-33-elicited modules (pp38/NF-κB) remained unaffected by co-stimulation of FcεRI/MRGPRX2. Collectively, the strong synergistic activity of IL-33 primarily results from the complementation of highly distinct modules following co-activation of the partner receptor rather than by altered signal strength of the same modules. Full article
(This article belongs to the Special Issue New Insights into Mast Cells Biology)
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Review

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19 pages, 760 KiB  
Review
Choroidal Mast Cells and Pathophysiology of Age-Related Macular Degeneration
by Sara Malih, Yong-Seok Song, Christine M. Sorenson and Nader Sheibani
Cells 2024, 13(1), 50; https://doi.org/10.3390/cells13010050 - 26 Dec 2023
Cited by 2 | Viewed by 2953
Abstract
Age-related macular degeneration (AMD) remains a leading cause of vision loss in elderly patients. Its etiology and progression are, however, deeply intertwined with various cellular and molecular interactions within the retina and choroid. Among the key cellular players least studied are choroidal mast [...] Read more.
Age-related macular degeneration (AMD) remains a leading cause of vision loss in elderly patients. Its etiology and progression are, however, deeply intertwined with various cellular and molecular interactions within the retina and choroid. Among the key cellular players least studied are choroidal mast cells, with important roles in immune and allergic responses. Here, we will review what is known regarding the pathophysiology of AMD and expand on the recently proposed intricate roles of choroidal mast cells and their activation in outer retinal degeneration and AMD pathogenesis. We will focus on choroidal mast cell activation, the release of their bioactive mediators, and potential impact on ocular oxidative stress, inflammation, and overall retinal and choroidal health. We propose an important role for thrombospondin-1 (TSP1), a major ocular angioinflammatory factor, in regulation of choroidal mast cell homeostasis and activation in AMD pathogenesis. Drawing from limited studies, this review underscores the need for further comprehensive studies aimed at understanding the precise roles changes in TSP1 levels and choroidal mast cell activity play in pathophysiology of AMD. We will also propose potential therapeutic strategies targeting these regulatory pathways, and highlighting the promise they hold for curbing AMD progression through modulation of mast cell activity. In conclusion, the evolving understanding of the role of choroidal mast cells in AMD pathogenesis will not only offer deeper insights into the underlying mechanisms but will also offer opportunities for development of novel preventive strategies. Full article
(This article belongs to the Special Issue New Insights into Mast Cells Biology)
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17 pages, 3181 KiB  
Review
Emerging Role of the Mast Cell–Microbiota Crosstalk in Cutaneous Homeostasis and Immunity
by Cameron Jackson Bosveld, Colin Guth, Nathachit Limjunyawong and Priyanka Pundir
Cells 2023, 12(22), 2624; https://doi.org/10.3390/cells12222624 - 14 Nov 2023
Cited by 4 | Viewed by 7316
Abstract
The skin presents a multifaceted microbiome, a balanced coexistence of bacteria, fungi, and viruses. These resident microorganisms are fundamental in upholding skin health by both countering detrimental pathogens and working in tandem with the skin’s immunity. Disruptions in this balance, known as dysbiosis, [...] Read more.
The skin presents a multifaceted microbiome, a balanced coexistence of bacteria, fungi, and viruses. These resident microorganisms are fundamental in upholding skin health by both countering detrimental pathogens and working in tandem with the skin’s immunity. Disruptions in this balance, known as dysbiosis, can lead to disorders like psoriasis and atopic dermatitis. Central to the skin’s defense system are mast cells. These are strategically positioned within the skin layers, primed for rapid response to any potential foreign threats. Recent investigations have started to unravel the complex interplay between these mast cells and the diverse entities within the skin’s microbiome. This relationship, especially during times of both balance and imbalance, is proving to be more integral to skin health than previously recognized. In this review, we illuminate the latest findings on the ties between mast cells and commensal skin microorganisms, shedding light on their combined effects on skin health and maladies. Full article
(This article belongs to the Special Issue New Insights into Mast Cells Biology)
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29 pages, 1325 KiB  
Review
Effects of Dietary Components on Mast Cells: Possible Use as Nutraceuticals for Allergies?
by Sina Kaag and Axel Lorentz
Cells 2023, 12(22), 2602; https://doi.org/10.3390/cells12222602 - 10 Nov 2023
Cited by 4 | Viewed by 4646
Abstract
Allergic diseases affect an estimated 30 percent of the world’s population. Mast cells (MC) are the key effector cells of allergic reactions by releasing pro-inflammatory mediators such as histamine, lipid mediators, and cytokines/chemokines. Components of the daily diet, including certain fatty acids, amino [...] Read more.
Allergic diseases affect an estimated 30 percent of the world’s population. Mast cells (MC) are the key effector cells of allergic reactions by releasing pro-inflammatory mediators such as histamine, lipid mediators, and cytokines/chemokines. Components of the daily diet, including certain fatty acids, amino acids, and vitamins, as well as secondary plant components, may have effects on MC and thus may be of interest as nutraceuticals for the prevention and treatment of allergies. This review summarizes the anti-inflammatory effects of dietary components on MC, including the signaling pathways involved, in in vitro and in vivo models. Butyrate, calcitriol, kaempferol, quercetin, luteolin, resveratrol, curcumin, and cinnamon extract were the most effective in suppressing the release of preformed and de novo synthesized mediators from MC or in animal models. In randomized controlled trials (RCT), vitamin D, quercetin, O-methylated epigallocatechin gallate (EGCG), resveratrol, curcumin, and cinnamon extract improved symptoms of allergic rhinitis (AR) and reduced the number of inflammatory cells in patients. However, strategies to overcome the poor bioavailability of these nutrients are an important part of current research. Full article
(This article belongs to the Special Issue New Insights into Mast Cells Biology)
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Other

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12 pages, 1102 KiB  
Commentary
Beyond Allergies—Updates on The Role of Mas-Related G-Protein-Coupled Receptor X2 in Chronic Urticaria and Atopic Dermatitis
by Liron Lerner, Magda Babina, Torsten Zuberbier and Katarina Stevanovic
Cells 2024, 13(3), 220; https://doi.org/10.3390/cells13030220 - 25 Jan 2024
Cited by 7 | Viewed by 2720
Abstract
Mast cells (MCs) are an important part of the immune system, responding both to pathogens and toxins, but they also play an important role in allergic diseases, where recent data show that non-IgE-mediated activation is also of relevance, especially in chronic urticaria (CU) [...] Read more.
Mast cells (MCs) are an important part of the immune system, responding both to pathogens and toxins, but they also play an important role in allergic diseases, where recent data show that non-IgE-mediated activation is also of relevance, especially in chronic urticaria (CU) and atopic dermatitis (AD). Skin MCs express Mas-related G-protein-coupled receptor X2 (MRGPRX2), a key protein in non-IgE-dependent MC degranulation, and its overactivity is one of the triggering factors for the above-mentioned diseases, making MRGPRX2 a potential therapeutic target. Reviewing the latest literature revealed our need to focus on the discovery of MRGPRX2 activators as well as the ongoing vast research towards finding specific MRGPRX2 inhibitors for potential therapeutic approaches. Most of these studies are in their preliminary stages, with one drug currently being investigated in a clinical trial. Future studies and improved model systems are needed to verify whether any of these inhibitors may have the potential to be the next therapeutic treatment for CU, AD, and other pseudo-allergic reactions. Full article
(This article belongs to the Special Issue New Insights into Mast Cells Biology)
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