E-Mail Alert

Add your e-mail address to receive forthcoming issues of this journal:

Journal Browser

Journal Browser

Special Issue "Mast Cells in Health and Disease"

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 (15 June 2019)

Special Issue Editors

Guest Editor
Prof. Gianni Marone

Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI); University of Naples Federico II, 80125 Napoli, Italy
Website 1 | Website 2 | E-Mail
Interests: basophils; mast cells; asthma; allergic rhinitis; eosinophils; macrophages; TSLP; common variable immunodeficiency; IL-33
Guest Editor
Dr. Gilda Varricchi

Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI); University of Naples Federico II, 80131 Napoli, Italy
Website | E-Mail
Interests: immunology; asthma; TSLP; mast cells; basophils; tumor immunology

Special Issue Information

Dear Colleagues,

Mast cells are hematopoietic cells that arise from pluripotent precursors in bone marrow. Mast cell progenitors circulate in the blood and complete their maturation in all vascularized tissues under the influence of local factors (e.g., cytokines, chemokines). Although mast cells are traditionally best known for their detrimental impact on allergic disorders, there is increasing evidence that they can also play homeostatic, protective, and immunoregulatory roles.

This Special Issue on “Mast Cells in Health and Disease” addresses the aforementioned immunological activities, receptor systems, activating stimuli, and signal transduction of mast cells. Furthermore, the role of mast cells in allergic disorders, mastocytosis and mast cell activation syndrome, autoimmune diseases, cardiometabolic disorders, infectious diseases, and cancer will be discussed.

We hope that this Special Issue will provide a platform for enhanced research on mast cell biology.

Prof. Gianni Marone
Dr. Gilda Varricchi
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 papers will be 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. International Journal of Molecular Sciences 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 1800 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

  • mast cells in allergic disorders
  • mast cell receptors
  • mast cell cytokines
  • mastocytosis
  • mast cells in autoimmune diseases
  • mast cells in cancer
  • mast cells in cardiometabolic disorders

Published Papers (12 papers)

View options order results:
result details:
Displaying articles 1-12
Export citation of selected articles as:

Research

Jump to: Review, Other

Open AccessArticle
Lipocalin 2: A New Antimicrobial in Mast Cells
Int. J. Mol. Sci. 2019, 20(10), 2380; https://doi.org/10.3390/ijms20102380
Received: 17 January 2019 / Revised: 10 April 2019 / Accepted: 24 April 2019 / Published: 14 May 2019
PDF Full-text (1857 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Mast cells (MCs) play a significant role in the innate immune defense against bacterial infection through the release of cytokines and antimicrobial peptides. However, their antimicrobial function is still only partially described. We therefore hypothesized that MCs express additional antimicrobial peptides. In this [...] Read more.
Mast cells (MCs) play a significant role in the innate immune defense against bacterial infection through the release of cytokines and antimicrobial peptides. However, their antimicrobial function is still only partially described. We therefore hypothesized that MCs express additional antimicrobial peptides. In this study, we used FANTOM 5 transcriptome data to identify for the first time that MCs express lipocalin 2 (LCN2), a known inhibitor of bacterial growth. Using MCs derived from mice which were deficient in LCN2, we showed that this antimicrobial peptide is an important component of the MCs’ antimicrobial activity against Escherichia coli (E. coli). Since sphingosine-1-phosphate receptors (S1PRs) on MCs are known to regulate their function during infections, we hypothesized that S1P could activate LCN2 production in MCs. Using an in vitro assay, we demonstrated that S1P enhances MCs antimicrobial peptide production and increases the capacity of MCs to directly kill S. aureus and E. coli via an LCN2 release. In conclusion, we showed that LCN2 is expressed by MCs and plays a role in their capacity to inhibit bacterial growth. Full article
(This article belongs to the Special Issue Mast Cells in Health and Disease)
Figures

Figure 1

Open AccessArticle
Tetrahydrocannabinol Reduces Hapten-Driven Mast Cell Accumulation and Persistent Tactile Sensitivity in Mouse Model of Allergen-Provoked Localized Vulvodynia
Int. J. Mol. Sci. 2019, 20(9), 2163; https://doi.org/10.3390/ijms20092163
Received: 28 March 2019 / Revised: 23 April 2019 / Accepted: 26 April 2019 / Published: 1 May 2019
PDF Full-text (1959 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Vulvodynia is a remarkably prevalent chronic pain condition of unknown etiology. An increase in numbers of vulvar mast cells often accompanies a clinical diagnosis of vulvodynia and a history of allergies amplifies the risk of developing this condition. We previously showed that repeated [...] Read more.
Vulvodynia is a remarkably prevalent chronic pain condition of unknown etiology. An increase in numbers of vulvar mast cells often accompanies a clinical diagnosis of vulvodynia and a history of allergies amplifies the risk of developing this condition. We previously showed that repeated exposures to oxazolone dissolved in ethanol on the labiar skin of mice led to persistent genital sensitivity to pressure and a sustained increase in labiar mast cells. Here we sensitized female mice to the hapten dinitrofluorobenzene (DNFB) dissolved in saline on their flanks, and subsequently challenged them with the same hapten or saline vehicle alone for ten consecutive days either on labiar skin or in the vaginal canal. We evaluated tactile ano-genital sensitivity, and tissue inflammation at serial timepoints. DNFB-challenged mice developed significant, persistent tactile sensitivity. Allergic sites showed mast cell accumulation, infiltration of resident memory CD8+CD103+ T cells, early, localized increases in eosinophils and neutrophils, and sustained elevation of serum Immunoglobulin E (IgE). Therapeutic intra-vaginal administration of Δ9-tetrahydrocannabinol (THC) reduced mast cell accumulation and tactile sensitivity. Mast cell-targeted therapeutic strategies may therefore provide new ways to manage and treat vulvar pain potentially instigated by repeated allergenic exposures. Full article
(This article belongs to the Special Issue Mast Cells in Health and Disease)
Figures

Graphical abstract

Open AccessArticle
A Transcriptomic Insight into the Impact of Colon Cancer Cells on Mast Cells
Int. J. Mol. Sci. 2019, 20(7), 1689; https://doi.org/10.3390/ijms20071689
Received: 8 March 2019 / Revised: 27 March 2019 / Accepted: 1 April 2019 / Published: 4 April 2019
PDF Full-text (1588 KB) | HTML Full-text | XML Full-text
Abstract
Mast cells (MCs) are one of the first immune cells recruited to a tumor. It is well recognized that MCs accumulate in colon cancer lesion and their density is associated with the clinical outcomes. However, the molecular mechanism of how colon cancer cells [...] Read more.
Mast cells (MCs) are one of the first immune cells recruited to a tumor. It is well recognized that MCs accumulate in colon cancer lesion and their density is associated with the clinical outcomes. However, the molecular mechanism of how colon cancer cells may modify MC function is still unclear. In this study, primary human MCs were generated from CD34+ progenitor cells and a 3D coculture model was developed to study the interplay between colon cancer cells and MCs. By comparing the transcriptomic profile of colon cancer-cocultured MCs versus control MCs, we identified a number of deregulated genes, such as MMP-2, VEGF-A, PDGF-A, COX2, NOTCH1 and ISG15, which contribute to the enrichment of cancer-related pathways. Intriguingly, pre-stimulation with a TLR2 agonist prior to colon cancer coculture induced upregulation of multiple interferon-inducible genes as well as MHC molecules in MCs. Our study provides an alternative approach to study the influence of colon cancer on MCs. The transcriptome signature of colon cancer-cocultured MCs may potentially reflect the mechanism of how colon cancer cells educate MCs to become pro-tumorigenic in the initial phase and how a subsequent inflammatory signal—e.g., TLR2 ligands—may modify their responses in the cancer milieu. Full article
(This article belongs to the Special Issue Mast Cells in Health and Disease)
Figures

Graphical abstract

Review

Jump to: Research, Other

Open AccessReview
Multidisciplinary Challenges in Mastocytosis and How to Address with Personalized Medicine Approaches
Int. J. Mol. Sci. 2019, 20(12), 2976; https://doi.org/10.3390/ijms20122976 (registering DOI)
Received: 26 March 2019 / Revised: 5 June 2019 / Accepted: 16 June 2019 / Published: 18 June 2019
PDF Full-text (281 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Mastocytosis is a hematopoietic neoplasm defined by abnormal expansion and focal accumulation of clonal tissue mast cells in various organ-systems. The disease exhibits a complex pathology and an equally complex clinical behavior. The classification of the World Health Organization (WHO) divides mastocytosis into [...] Read more.
Mastocytosis is a hematopoietic neoplasm defined by abnormal expansion and focal accumulation of clonal tissue mast cells in various organ-systems. The disease exhibits a complex pathology and an equally complex clinical behavior. The classification of the World Health Organization (WHO) divides mastocytosis into cutaneous forms, systemic variants, and localized mast cell tumors. In >80% of patients with systemic mastocytosis (SM), a somatic point mutation in KIT at codon 816 is found. Whereas patients with indolent forms of the disease have a normal or near-normal life expectancy, patients with advanced mast cell neoplasms, including aggressive SM and mast cell leukemia, have a poor prognosis with short survival times. In a majority of these patients, multiple somatic mutations and/or an associated hematologic neoplasm, such as a myeloid leukemia, may be detected. Independent of the category of mastocytosis and the serum tryptase level, patients may suffer from mediator-related symptoms and/or osteopathy. Depending on the presence of co-morbidities, the symptomatology in such patients may be mild, severe or even life-threatening. Most relevant co-morbidities in such patients are IgE-dependent allergies, psychiatric, psychological or mental problems, and vitamin D deficiency. The diagnosis and management of mastocytosis is an emerging challenge in clinical practice and requires vast knowledge, a multidisciplinary approach, and personalized medicine procedures. In this article, the current knowledge about mastocytosis is reviewed with special emphasis on the multidisciplinary aspects of the disease and related challenges in daily practice. Full article
(This article belongs to the Special Issue Mast Cells in Health and Disease)
Open AccessReview
Mast Cells in Viral, Bacterial, and Fungal Infection Immunity
Int. J. Mol. Sci. 2019, 20(12), 2851; https://doi.org/10.3390/ijms20122851
Received: 26 April 2019 / Revised: 31 May 2019 / Accepted: 11 June 2019 / Published: 12 June 2019
PDF Full-text (1836 KB) | HTML Full-text | XML Full-text
Abstract
Mast cells are granule-rich immune cells that are distributed throughout the body in areas where microorganisms typically reside, such as mucosal tissues and the skin, as well as connective tissues. It is well known that mast cells have significant roles in IgE-mediated conditions, [...] Read more.
Mast cells are granule-rich immune cells that are distributed throughout the body in areas where microorganisms typically reside, such as mucosal tissues and the skin, as well as connective tissues. It is well known that mast cells have significant roles in IgE-mediated conditions, such as anaphylaxis, but, because of their location, it is also thought that mast cells act as innate immune cells against pathogens and initiate defensive immune responses. In this review, we discuss recent studies focused on mast cell interactions with flaviviruses and Candida albicans, and mast cell function in the cecal ligation and puncture model of sepsis. We selected these studies because they are clear examples of how mast cells can either promote host resistance to infection, as previously proposed, or contribute to a dysregulated host response that can increase host morbidity and mortality. Importantly, we can distill from these studies that the contribution of mast cells to infection outcomes depends in part on the infection model, including the genetic approach used to assess the influence of mast cells on host immunity, the species in which mast cells are studied, and the differential contribution of mast cell subtypes to immunity. Accordingly, we think that this review highlights the complexity of mast cell biology in the context of innate immune responses. Full article
(This article belongs to the Special Issue Mast Cells in Health and Disease)
Figures

Figure 1

Open AccessReview
Role of Mast Cell-Derived Adenosine in Cancer
Int. J. Mol. Sci. 2019, 20(10), 2603; https://doi.org/10.3390/ijms20102603
Received: 4 May 2019 / Revised: 23 May 2019 / Accepted: 24 May 2019 / Published: 27 May 2019
PDF Full-text (1225 KB) | HTML Full-text | XML Full-text
Abstract
Accumulating evidence has highlighted the accumulation of mast cells (MCs) in tumors. However, their impact on tumor development remained controversial. Indeed, cumulative data indicate an enigmatic role for MCs in cancer, whereby depending on the circumstances, which still need to be resolved, MCs [...] Read more.
Accumulating evidence has highlighted the accumulation of mast cells (MCs) in tumors. However, their impact on tumor development remained controversial. Indeed, cumulative data indicate an enigmatic role for MCs in cancer, whereby depending on the circumstances, which still need to be resolved, MCs function to promote or restrict tumor growth. By responding to multiple stimuli MCs release multiple inflammatory mediators, that contribute to the resolution of infection and resistance to envenomation, but also have the potency to promote or inhibit malignancy. Thus, MCs seem to possess the power to define tumor projections. Given this remarkable plasticity of MC responsiveness, there is an urgent need of understanding how MCs are activated in the tumor microenvironment (TME). We have recently reported on the direct activation of MCs upon contact with cancer cells by a mechanism involving an autocrine formation of adenosine and signaling by the A3 adenosine receptor. Here we summarized the evidence on the role of adenosine signaling in cancer, in MC mediated inflammation and in the MC-cancer crosstalk. Full article
(This article belongs to the Special Issue Mast Cells in Health and Disease)
Figures

Graphical abstract

Open AccessReview
PD-L1 Expression in Mastocytosis
Int. J. Mol. Sci. 2019, 20(9), 2362; https://doi.org/10.3390/ijms20092362
Received: 8 April 2019 / Revised: 1 May 2019 / Accepted: 4 May 2019 / Published: 13 May 2019
PDF Full-text (2428 KB) | HTML Full-text | XML Full-text
Abstract
Programmed death 1 (PD-1), when activated by its ligands PD-L1 and PD-L2, suppresses active immune cells in normal immune regulation to limit autoimmunity and, in tumors, as a mechanism of immune evasion. PD-L1 expression has been described as both a prognostic and predictive [...] Read more.
Programmed death 1 (PD-1), when activated by its ligands PD-L1 and PD-L2, suppresses active immune cells in normal immune regulation to limit autoimmunity and, in tumors, as a mechanism of immune evasion. PD-L1 expression has been described as both a prognostic and predictive marker in many solid and hematologic neoplasms, as targeted therapies against the PD-1/PD-L1 interaction have gained clinical importance. PD-L1 expression has been assessed in a few studies on mastocytosis. We review this literature and the need for further investigation of the tumor-immune interaction in mastocytosis. Full article
(This article belongs to the Special Issue Mast Cells in Health and Disease)
Figures

Figure 1

Open AccessReview
MicroRNA Involvement in Allergic and Non-Allergic Mast Cell Activation
Int. J. Mol. Sci. 2019, 20(9), 2145; https://doi.org/10.3390/ijms20092145
Received: 31 March 2019 / Revised: 28 April 2019 / Accepted: 29 April 2019 / Published: 30 April 2019
PDF Full-text (862 KB) | HTML Full-text | XML Full-text
Abstract
Allergic inflammation is accompanied by the coordinated expression of numerous genes and proteins that initiate, sustain, and propagate immune responses and tissue remodeling. MicroRNAs (miRNAs) are a large class of small regulatory molecules that are able to control the translation of target mRNAs [...] Read more.
Allergic inflammation is accompanied by the coordinated expression of numerous genes and proteins that initiate, sustain, and propagate immune responses and tissue remodeling. MicroRNAs (miRNAs) are a large class of small regulatory molecules that are able to control the translation of target mRNAs and consequently regulate various biological processes at the posttranscriptional level. MiRNA profiles have been identified in multiple allergic inflammatory diseases and in the tumor microenvironment. Mast cells have been found to co-localize within the above conditions. More specifically, in addition to being essential in initiating the allergic response, mast cells play a key role in both innate and adaptive immunity as well as in modulating tumor growth. This review summarizes the possible role of various miRNAs in the above-mentioned processes wherein mast cells have been found to be involved. Understanding the role of miRNAs in mast cell activation and function may serve as an important tool in developing diagnostic as well as therapeutic approaches in mast cell-dependent pathological conditions. Full article
(This article belongs to the Special Issue Mast Cells in Health and Disease)
Figures

Graphical abstract

Open AccessReview
Mast Cells, Angiogenesis and Lymphangiogenesis in Human Gastric Cancer
Int. J. Mol. Sci. 2019, 20(9), 2106; https://doi.org/10.3390/ijms20092106
Received: 20 March 2019 / Revised: 15 April 2019 / Accepted: 19 April 2019 / Published: 29 April 2019
PDF Full-text (1142 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Gastric cancer is diagnosed in nearly one million new patients each year and it remains the second leading cause of cancer-related deaths worldwide. Although gastric cancer represents a heterogeneous group of diseases, chronic inflammation has been shown to play a role in tumorigenesis. [...] Read more.
Gastric cancer is diagnosed in nearly one million new patients each year and it remains the second leading cause of cancer-related deaths worldwide. Although gastric cancer represents a heterogeneous group of diseases, chronic inflammation has been shown to play a role in tumorigenesis. Cancer development is a multistep process characterized by genetic and epigenetic alterations during tumour initiation and progression. The stromal microenvironment is important in maintaining normal tissue homeostasis or promoting tumour development. A plethora of immune cells (i.e., lymphocytes, macrophages, mast cells, monocytes, myeloid-derived suppressor cells, Treg cells, dendritic cells, neutrophils, eosinophils, natural killer (NK) and natural killer T (NKT) cells) are components of gastric cancer microenvironment. Mast cell density is increased in gastric cancer and there is a correlation with angiogenesis, the number of metastatic lymph nodes and the survival of these patients. Mast cells exert a protumorigenic role in gastric cancer through the release of angiogenic (VEGF-A, CXCL8, MMP-9) and lymphangiogenic factors (VEGF-C and VEGF-F). Gastric mast cells express the programmed death ligands (PD-L1 and PD-L2) which are relevant as immune checkpoints in cancer. Several clinical undergoing trials targeting immune checkpoints could be an innovative therapeutic strategy in gastric cancer. Elucidation of the role of subsets of mast cells in different human gastric cancers will demand studies of increasing complexity beyond those assessing merely mast cell density and microlocalization. Full article
(This article belongs to the Special Issue Mast Cells in Health and Disease)
Figures

Figure 1

Open AccessReview
Mast Cells in Early Rheumatoid Arthritis
Int. J. Mol. Sci. 2019, 20(8), 2040; https://doi.org/10.3390/ijms20082040
Received: 4 April 2019 / Revised: 18 April 2019 / Accepted: 22 April 2019 / Published: 25 April 2019
PDF Full-text (1475 KB) | HTML Full-text | XML Full-text
Abstract
Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by inflammation of the synovial membrane, with thickening of the synovial layer, cellular hyperplasia, and infiltration of immune cells. Mast cells (MCs) are cells of the innate immunity present in healthy synovia and [...] Read more.
Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by inflammation of the synovial membrane, with thickening of the synovial layer, cellular hyperplasia, and infiltration of immune cells. Mast cells (MCs) are cells of the innate immunity present in healthy synovia and part of the cellular hyperplasia characterizing RA synovitis. Although their presence in synovia has been well described, the exact functions and the correlation of MCs with disease development and progression have been debated, particularly because of contradictory data obtained in animal models and from patients with longstanding disease. Here, we present a revision of the literature on MCs in RA, including the most recent observations obtained from patients with early RA, indicating MCs as relevant markers of disease severity in early RA. Full article
(This article belongs to the Special Issue Mast Cells in Health and Disease)
Figures

Graphical abstract

Open AccessReview
Mast Cells and Angiogenesis in Human Plasma Cell Malignancies
Int. J. Mol. Sci. 2019, 20(3), 481; https://doi.org/10.3390/ijms20030481
Received: 13 December 2018 / Revised: 18 January 2019 / Accepted: 21 January 2019 / Published: 23 January 2019
Cited by 1 | PDF Full-text (1465 KB) | HTML Full-text | XML Full-text
Abstract
Bone marrow angiogenesis plays an important role in the pathogenesis and progression of hematological malignancies. It is well known that tumor microenvironment promotes tumor angiogenesis, proliferation, invasion, and metastasis, and also mediates mechanisms of therapeutic resistance. An increased number of mast cells has [...] Read more.
Bone marrow angiogenesis plays an important role in the pathogenesis and progression of hematological malignancies. It is well known that tumor microenvironment promotes tumor angiogenesis, proliferation, invasion, and metastasis, and also mediates mechanisms of therapeutic resistance. An increased number of mast cells has been demonstrated in angiogenesis associated with hematological tumors. In this review we focused on the role of mast cells in angiogenesis in human plasma cell malignancies. In this context, mast cells might act as a new target for the adjuvant treatment of these tumors through the selective inhibition of angiogenesis, tissue remodeling and tumor-promoting molecules, permitting the secretion of cytotoxic cytokines and preventing mast cell-mediated immune suppression. Full article
(This article belongs to the Special Issue Mast Cells in Health and Disease)
Figures

Figure 1

Other

Jump to: Research, Review

Open AccessOpinion
Role of Leukotriene B4 Receptor-2 in Mast Cells in Allergic Airway Inflammation
Int. J. Mol. Sci. 2019, 20(12), 2897; https://doi.org/10.3390/ijms20122897
Received: 30 May 2019 / Revised: 12 June 2019 / Accepted: 12 June 2019 / Published: 14 June 2019
PDF Full-text (299 KB) | HTML Full-text | XML Full-text
Abstract
Mast cells are effector cells in the immune system that play an important role in the allergic airway inflammation. Recently, it was reported that BLT2, a low-affinity leukotriene (LT) B4 receptor, plays a pivotal role in the pathogenesis of allergic airway inflammation [...] Read more.
Mast cells are effector cells in the immune system that play an important role in the allergic airway inflammation. Recently, it was reported that BLT2, a low-affinity leukotriene (LT) B4 receptor, plays a pivotal role in the pathogenesis of allergic airway inflammation through its action in mast cells. We observed that highly elevated expression levels of BLT2 are critical for the pathogenesis leading to allergic airway inflammation, and that if BLT2 expression is downregulated by siBLT2-mediated knockdown, allergic inflammation is dramatically alleviated. Furthermore, we demonstrated that BLT2 mediates the synthesis of vascular endothelial growth factor (VEGF) and Th2 cytokines, such as interleukin (IL)-13, in mast cells during allergic inflammation. Based on the critical roles of BLT2 in mast cells in allergic inflammation, anti-BLT2 strategies could contribute to the development of new therapies for allergic airway inflammation. Full article
(This article belongs to the Special Issue Mast Cells in Health and Disease)
Figures

Figure 1

Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top