BAT and MAT for diagnosis of peanut allergy: A systematic review and meta-analysis.

Basophil activation test (BAT) or the mast cell activation test (MAT) are two in vitro tests that are currently being studied in food allergy as diagnostic tools as an alternative to oral food challenges (OFCs). We conducted a meta-analysis on BAT and MAT, assessing their specificity and sensitivity in diagnosing peanut allergy. Six databases were searched for studies on patients suspected of having peanut allergy. Studies using BAT or MAT to peanut extract and/or component as diagnostic tools with results given in percentage of CD63 activation were included in this meta-analysis. Study quality was evaluated with the QUADAS-2 tool. On the 11 studies identified, eight focused exclusively on children, while three included a mixed population of adults and children. Only one study provided data on MAT, precluding us from conducting a statistical analysis. The diagnostic accuracy of BAT was higher when stimulated with peanut extract rather than Ara h 2 with a pooled specificity of 96% (95% CI: 0.89-0.98) and sensitivity of 0.86 (95% CI: 0.74-0.93). The sensitivity and specificity of BATs in discriminating between allergic and sensitized patients were studied as well, with pooled analysis revealing a sensitivity of 0.86 (95% CI: 0.74; 0.93) and a specificity of 0.97 (95% CI: 0.94, 0.98). BATs, when stimulated with peanut extracts, exhibit a satisfactory sensitivity and specificity for the diagnosis of peanut allergy and can help to discriminate between allergic individuals and those only sensitized to peanuts. More investigations on the potential for MATs diagnostic methods are warranted.

MRGPRX2 antagonist GE1111 attenuated DNFB-induced atopic dermatitis in mice by reducing inflammatory cytokines and restoring skin integrity.

Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterised by itching, erythema, and epidermal barrier dysfunction. The pathogenesis of AD is complex and multifactorial; however,mast cell (MC) activation has been reported to be one of the crucial mechanisms in the pathogenesis of AD. The MC receptor Mas related G protein-coupled receptor-X2 (MRGPRX2) has been identified as a prominent alternative receptor to the IgE receptor in causing MC activation and the subsequent release of inflammatory mediators. The current study aimed to evaluate the therapeutic effect of a novel small molecule MRGPRX2 antagonist GE1111 in AD using in vitro and in vivo approaches. Methods: We developed an in vitro cell culture disease model by using LAD-2 MC, HaCaT keratinocytes and RAW 264.7 macrophage cell lines. We challenged keratinocytes and macrophage cells with CST-14 treated MC supernatant in the presence and absence of GE1111 and measured the expression of tight junction protein claudin 1, inflammatory cytokines and macrophage phagocytosis activity through immunohistochemistry, western blotting, RT-qPCR and fluorescence imaging techniques. In addition to this, we developed a DFNB-induced AD model in mice and evaluated the protective effect and underlying mechanism of GE1111. Results and Discussion: Our in vitro findings demonstrated a potential therapeutic effect of GE1111, which inhibits the expression of TSLP, IL-13, MCP-1, TNF-a, and IL-1ß in MC and keratinocytes. In addition to this, GE1111 was able to preserve the expression of claudin 1 in keratinocytes and the phagocytotic activity of macrophage cells. The in vivo results demonstrated that GE1111 treatment significantly reduced phenotypic changes associated with AD (skin thickening, scaling, erythema and epidermal thickness). Furthermore, immunohistochemical analysis demonstrated that GE1111 treatment preserved the expression of the tight junction protein Involucrin and reduced the expression of the inflammatory mediator periostin in the mouse model of AD. These findings were supported by gene and protein expression analysis, where GE1111 treatment reduced the expression of TSLP, IL-13, and IL-1ß, as well as downstream signalling pathways of MRGPRX2 in AD skin lesions. In conclusion, our findings provide compelling in vitro and in vivo evidence supporting the contribution of MRGPRX2-MC interaction with keratinocytes and macrophages in the pathogenesis of AD.

Basophil-Derived IL-4 and IL-13 Protect Intestinal Barrier Integrity and Control Bacterial Translocation during Malaria.

Our previous work demonstrated that basophils regulate a suite of malaria phenotypes, including intestinal mastocytosis and permeability, the immune response to infection, gametocytemia, and parasite transmission to the malaria mosquito Anopheles stephensi. Given that activated basophils are primary sources of the regulatory cytokines IL-4 and IL-13, we sought to examine the contributions of these mediators to basophil-dependent phenotypes in malaria. We generated mice with basophils depleted for IL-4 and IL-13 (baso IL-4/IL-13 (-)) and genotype controls (baso IL-4/IL-13 (+)) by crossing mcpt8-Cre and Il4/Il13fl/fl mice and infected them with Plasmodium yoelii yoelii 17XNL. Conditional deletion was associated with ileal mastocytosis and mast cell (MC) activation, increased intestinal permeability, and increased bacterial 16S levels in blood, but it had no effect on neutrophil activation, parasitemia, or transmission to A. stephensi. Increased intestinal permeability in baso IL-4/IL-13 (-) mice was correlated with elevated plasma eotaxin (CCL11), a potent eosinophil chemoattractant, and increased ileal MCs, proinflammatory IL-17A, and the chemokines MIP-1α (CCL3) and MIP-1ß (CCL4). Blood bacterial 16S copies were positively but weakly correlated with plasma proinflammatory cytokines IFN-γ and IL-12p40, suggesting that baso IL-4/IL-13 (-) mice failed to control bacterial translocation into the blood during malaria infection. These observations suggest that basophil-derived IL-4 and IL-13 do not contribute to basophil-dependent regulation of parasite transmission, but these cytokines do orchestrate protection of intestinal barrier integrity after P. yoelii infection. Specifically, basophil-dependent IL-4/IL-13 control MC activation and prevent infection-induced intestinal barrier damage and bacteremia, perhaps via regulation of eosinophils, macrophages, and Th17-mediated inflammation.

A new superhero, the intraepithelial mast cell, joins the "Guardians of the Gut".

The intestinal epithelium interacts with immune cells to support tissue homeostasis and coordinate responses against pathogens. In this issue of Immunity, Yang et al. unveil a central role for mast cell-epithelial cell interactions in orchestrating protective type 2 immune responses following intestinal helminth infection.

Mast cell-derived interleukin-4 mediates activation of dendritic cell during toll-like receptor 2-mediated inflammation.

Introduction: During an innate inflammation, immune cells form distinct pro- and anti-inflammatory regions around pathogen-containing core-regions. Mast cells are localized in an anti-inflammatory microenvironment during the resolution of an innate inflammation, suggesting antiinflammatory roles of these cells. Methods: High-content imaging was used to investigated mast cell-dependent changes in the regional distribution of immune cells during an inflammation, induced by the toll-like receptor (TLR)-2 agonist zymosan. Results: The distance between the zymosan-containing core-region and the anti-inflammatory region, described by M2-like macrophages, increased in mast cell-deficient mice. Absence of mast cells abolished dendritic cell (DC) activation, as determined by CD86-expression and localized the DCs in greater distance to zymosan particles. The CD86- DCs had a higher expression of the pro-inflammatory interleukins (IL)-1ß and IL-12/23p40 as compared to activated CD86+ DCs. IL-4 administration restored CD86 expression, cytokine expression profile and localization of the DCs in mast cell-deficient mice. The IL-4 effects were mast cell-specific, since IL-4 reduction by eosinophil depletion did not affect activation of DCs. Discussion: We found that mast cells induce DC activation selectively at the site of inflammation and thereby determine their localization within the inflammation. Overall, mast cells have antiinflammatory functions in this inflammation model and limit the size of the pro-inflammatory region surrounding the zymosan-containing core region.

Novel IgE crosslinking-induced luciferase expression method using human-rat chimeric IgE receptor-carrying mast cells.

BACKGROUND: The measurement of antigen-specific serum IgE is common in clinical assessments of type I allergies. However, the interaction between antigens and IgE won't invariably trigger mast cell activation. We previously developed the IgE crosslinking-induced luciferase expression (EXiLE) method using the RS-ATL8 mast cell line; however, the method may not be sensitive enough in some cases. METHODS: In this study, we introduced an NF-AT-regulated luciferase reporter gene into the RBL-2H3 rat mast cell line and expressed a chimeric high-affinity IgE receptor (FcεRI) α chain gene, comprising an extracellular domain from humans and transmembrane/intracellular domains from rats. RESULTS: We generated multiple clones expressing the chimeric receptor. Based on their responsiveness and proliferation, we selected the HuRa-40 clone. This cell line exhibited significantly elevated human α chain expression compared to RS-ATL8 cells, demonstrating a 10-fold enhancement of antigen-specific reactivity. Reproducibility across different batches and operators was excellent. Moreover, we observed a detectable response inhibition by an anti-allergy drugs (omalizumab and cyclosporin A). CONCLUSIONS: HuRa-40 cells-which carry the human-rat chimeric IgE receptor-comprise a valuable reporter cell line for the EXiLE method. Their versatility extends to various applications and facilitates high-throughput screening of anti-allergy drugs.

Mast cell degranulation and bradykinin-induced angioedema - searching for the missing link.

Initiation of the bradykinin generation cascade is responsible for the occurrence of attacks in some types of angioedema without wheals. Hereditary angioedema due to C1 inhibitor deficiency (HAE-C1-INH) is one such clinical entity. In this paper, we explore the existing evidence that mast cells (MCs) degranulation may contribute to the activation of the kallikrein-kinin system cascade, followed by bradykinin formation and angioedema. We present the multidirectional effects of MC-derived heparin and other polyanions on the major components of the kinin-kallikrein system, particularly on the factor XII activation. Although, bradykinin- and histamine-mediated symptoms are distinct clinical phenomena, they share some common features, such as some similar triggers and a predilection to occur at sites where mast cells reside, namely the skin and mucous membranes. In addition, recent observations indicate a high incidence of hypersensitivity reactions associated with MC degranulation in the HAE-C1-INH patient population. However, not all of these can be explained by IgE-dependent mechanisms. Mast cell-related G protein-coupled receptor-X2 (MRGPRX2), which has recently attracted scientific interest, may be involved in the activation of MCs through a different pathway. Therefore, we reviewed MRGPRX2 ligands that HAE-C1-INH patients may be exposed to in their daily lives and that may affect MCs degranulation. We also discussed the known inter- and intra-individual variability in the course of HAE-C1-INH in relation to factors responsible for possible variability in the strength of the response to MRGPRX2 receptor stimulation. The above issues raise several questions for future research. It is not known to what extent a prophylactic or therapeutic intervention targeting the pathways of one mechanism (mast cell degranulation) may affect the other (bradykinin production), or whether the number of mast cells at a specific body site and their reactivity to triggers such as pressure, allergens or MRGPRX2 agonists may influence the occurrence of HAE-C1-INH attacks at that site.

The role of Interleukin-21 (IL-21) in allergic disorders: Biological insights and regulatory mechanisms.

In recent decades, allergic diseases subsequent from an IgE-mediated response to specific allergens have become a progressively public chronic disease worldwide. They have shaped an important medical and socio-economic burden. A significant proportion of allergic disorders are branded via a form 2 immune response relating Th2 cells, type 2 natural lymphoid cells, mast cells and eosinophils. Interleukin-21 (IL-21) is a participant of the type-I cytokine family manufactured through numerous subsets of stimulated CD4+ T cells and uses controlling properties on a diversity of immune cells. Increasingly, experimental sign suggests a character for IL-21 in the pathogenesis of numerous allergic disorders. The purpose of this review is to discuss the biological properties of IL-21 and to summaries current developments in its role in the regulation of allergic disorders.

Inhibitory effect of phellodendrine on C48/80-induced allergic reaction in vitro and in vivo.

The incidence of allergic reactions has risen steadily in recent years, prompting growing interest in the identification of efficacious and safe natural compounds that can prevent or treat allergic diseases. Phellodendron amurense Rupr. has long been applied as a treatment for allergic diseases, whose primary component is phellodendrine. However, the efficacy of phellodendrine as a treatment for allergic diseases remains to be assessed. Mast cells are the primary effectors of allergic reactions, which are not only activated by IgE-dependent pathway, but also by IgE-independent pathways via human MRGPRX2, rat counterpart MRGPRB3. As such, this study explored the effect and mechanism of phellodendrine through this family receptors in treating allergic diseases in vitro and in vivo. These analyses revealed that phellodendrine administration was sufficient to protect against C48/80-induced foot swelling and Evans blue exudation in mice, and suppressed C48/80-induced RBL-2H3 rat basophilic leukemia cells degranulation, and ß-HEX, HIS, IL-4, and TNF-α release. Moreover, phellodendrine could reduce the mRNA expression of MRGPRB3 and responsiveness of MRGPRX2 by altering its structure. It was able to decrease Ca2+ levels, phosphorylation levels of CaMK, PLCß1, PKC, ERK, JNK, p38, and p65, and inhibit the degradation of IκB-α. These analyses indicate that berberine inhibits the activation of PLC and downregulates the release of Ca2+ in the endoplasmic reticulum by altering the conformation of MRGPRB3/MRGPRX2 protein, thereby inhibiting the activation of PKC and subsequently inhibiting downstream MAPK and NF-κB signaling, ultimately suppressing allergic reactions. There may thus be further value in studies focused on developing phellodendrine as a novel anti-allergic drug.

The immune and microbial homeostasis determines the Candida-mast cells cross-talk in celiac disease.

Celiac disease (CD) is an autoimmune enteropathy resulting from an interaction between diet, genome, and immunity. Although many patients respond to a gluten-free diet, in a substantive number of individuals, the intestinal injury persists. Thus, other factors might amplify the ongoing inflammation. Candida albicans is a commensal fungus that is well adapted to the intestinal life. However, specific conditions increase Candida pathogenicity. The hypothesis that Candida may be a trigger in CD has been proposed after the observation of similarity between a fungal wall component and two CD-related gliadin T-cell epitopes. However, despite being implicated in intestinal disorders, Candida may also protect against immune pathologies highlighting a more intriguing role in the gut. Herein, we postulated that a state of chronic inflammation associated with microbial dysbiosis and leaky gut are favorable conditions that promote C. albicans pathogenicity eventually contributing to CD pathology via a mast cells (MC)-IL-9 axis. However, the restoration of immune and microbial homeostasis promotes a beneficial C. albicans-MC cross-talk favoring the attenuation of CD pathology to alleviate CD pathology and symptoms.

[Mast Cell-Neutrophil Communication Regulates Allergic Diseases].

Allergic diseases (e.g., food allergies) are a growing problem, with increasing numbers of individuals experiencing them worldwide. Congruently, the adverse reactions (e.g., anaphylaxis) associated with the administration of vaccines against emerging infectious diseases such as coronavirus disease 2019 (COVID-19) have become a familiar problem. Allergic diseases, which have a wide variety of symptoms, are difficult to prevent or cure; treatment is currently limited to therapeutic drugs or allergen immunotherapy. Therefore, elucidating new allergic regulatory factors that control the allergic (i.e., mast cell) responses is important. While investigating the regulatory mechanisms of the wide range of allergic responses of mast cells, we found that the affinity of allergens to immunoglobin E (IgE) regulates allergic inflammation through the differences in the secretory responses of mast cells and the types and interactions of the cells infiltrating the tissues. Here, we present our recent findings regarding the affinity of allergens to IgE in regulating allergic inflammation, heterogeneous secretory granules inducing diverse secretory responses, and mast cells interacting with neutrophils, thereby regulating the various allergic responses.

Se-rich tea polysaccharide extracted by high hydrostatic pressure attenuated anaphylaxis by improving gut microbiota and metabolic regulation.

Selenium-rich tea polysaccharides (Se-TPS) were extracted via high hydrostatic pressure technology with a pressure of 400 MPa (200-500 MPa) for 10 min (3-20 min) at a material-to-solvent ratio of 1:40 (1:20-1:50). Subsequently, Se-TPS1-4 were isolated and purified, with Se-TPS3-4 as the main components. A spectral analysis proved that Se, which has antioxidant activity, existed. An in vitro study found that among Se-TPS, Se-TPS3-4 attenuated the release of ß-hexosaminidase, histamine, and interleukin (IL)-4. Furthermore, in vivo experiments revealed that treatment with Se-TPS downregulated IL-4 levels and upregulated TGF-ß and interferon-γ levels to improve imbalanced Th1/Th2 immunity in tropomyosin-sensitized mice. Moreover, Se-TPS promoted Lactobacillus and norank_f_Muribaculaceaek growth and upregulated metabolites such as genipin and coniferyl alcohol. Overall, these results showed the strong anti-allergy potential of Se-TPS by regulating mast cell-mediated allergic inflammatory responses and microbiota regulation, highlighting the potential of Se-TPS as a novel therapeutic agent to regulate allergy-associated metabolic disorders.

Mast cells: a novel therapeutic avenue for cardiovascular diseases?

Mast cells are tissue-resident immune cells strategically located in different compartments of the normal human heart (the myocardium, pericardium, aortic valve, and close to nerves) as well as in atherosclerotic plaques. Cardiac mast cells produce a broad spectrum of vasoactive and proinflammatory mediators, which have potential roles in inflammation, angiogenesis, lymphangiogenesis, tissue remodelling, and fibrosis. Mast cells release preformed mediators (e.g. histamine, tryptase, and chymase) and de novo synthesized mediators (e.g. cysteinyl leukotriene C4 and prostaglandin D2), as well as cytokines and chemokines, which can activate different resident immune cells (e.g. macrophages) and structural cells (e.g. fibroblasts and endothelial cells) in the human heart and aorta. The transcriptional profiles of various mast cell populations highlight their potential heterogeneity and distinct gene and proteome expression. Mast cell plasticity and heterogeneity enable these cells the potential for performing different, even opposite, functions in response to changing tissue contexts. Human cardiac mast cells display significant differences compared with mast cells isolated from other organs. These characteristics make cardiac mast cells intriguing, given their dichotomous potential roles of inducing or protecting against cardiovascular diseases. Identification of cardiac mast cell subpopulations represents a prerequisite for understanding their potential multifaceted roles in health and disease. Several new drugs specifically targeting human mast cell activation are under development or in clinical trials. Mast cells and/or their subpopulations can potentially represent novel therapeutic targets for cardiovascular disorders.

Intraepithelial mast cells drive gasdermin C-mediated type 2 immunity.

A specialized population of mast cells residing within epithelial layers, currently known as intraepithelial mast cells (IEMCs), was originally observed over a century ago, yet their physiological functions have remained enigmatic. In this study, we unveil an unexpected and crucial role of IEMCs in driving gasdermin C-mediated type 2 immunity. During helminth infection, αEß7 integrin-positive IEMCs engaged in extensive intercellular crosstalk with neighboring intestinal epithelial cells (IECs). Through the action of IEMC-derived proteases, gasdermin C proteins intrinsic to the epithelial cells underwent cleavage, leading to the release of a critical type 2 cytokine, interleukin-33 (IL-33). Notably, mast cell deficiency abolished the gasdermin C-mediated immune cascade initiated by epithelium. These findings shed light on the functions of IEMCs, uncover a previously unrecognized phase of type 2 immunity involving mast cell-epithelial cell crosstalk, and advance our understanding of the cellular mechanisms underlying gasdermin C activation.

Validation of mitochondrial biomarkers and immune dynamics in polycystic ovary syndrome.

PROBLEM: Polycystic ovary syndrome (PCOS), a prevalent endocrine-metabolic disorder, presents considerable therapeutic challenges due to its complex and elusive pathophysiology. METHOD OF STUDY: We employed three machine learning algorithms to identify potential biomarkers within a training dataset, comprising GSE138518, GSE155489, and GSE193123. The diagnostic accuracy of these biomarkers was rigorously evaluated using a validation dataset using area under the curve (AUC) metrics. Further validation in clinical samples was conducted using PCR and immunofluorescence techniques. Additionally, we investigate the complex interplay among immune cells in PCOS using CIBERSORT to uncover the relationships between the identified biomarkers and various immune cell types. RESULTS: Our analysis identified ACSS2, LPIN1, and NR4A1 as key mitochondria-related biomarkers associated with PCOS. A notable difference was observed in the immune microenvironment between PCOS patients and healthy controls. In particular, LPIN1 exhibited a positive correlation with resting mast cells, whereas NR4A1 demonstrated a negative correlation with monocytes in PCOS patients. CONCLUSION: ACSS2, LPIN1, and NR4A1 emerge as PCOS-related diagnostic biomarkers and potential intervention targets, opening new avenues for the diagnosis and management of PCOS.

Involvement of Mast Cells in the Pathology of COVID-19: Clinical and Laboratory Parallels.

Recent studies suggested the potential role of mast cells (MCs) in the pathology of coronavirus disease 2019 (COVID-19). However, the precise description of the MCs' activation and the engagement of their proteases is still missing. The objective of this study was to further reveal the importance of MCs and their proteases (chymase, tryptase, and carboxypeptidase A3 (CPA3)) in the development of lung damage in patients with COVID-19. This study included 55 patients who died from COVID-19 and 30 controls who died from external causes. A histological analysis of the lung parenchyma was carried out to assess the protease profiles and degranulation activity of MCs. In addition, we have analyzed the general blood test, coagulogram, and C-reactive protein. The content of tryptase-positive MCs (Try-MCs) in the lungs of patients with COVID-19 was higher than in controls, but their degranulation activity was lower. The indicators of chymase-positive MCs (Chy-MCs) were significantly lower than in the controls, while the content of CPA3-positive MCs (CPA3-MCs) and their degranulation activity were higher in patients with COVID-19. In addition, we have demonstrated the existence of correlations (positive/negative) between the content of Try-MCs, Chy-MCs, and CPA3-MCs at different states of their degranulation and presence (co-adjacent/single) and the levels of various immune cells (neutrophils, eosinophils, basophils, and monocytes) and other important markers (blood hemoglobin, activated partial thromboplastin time (aPTT), international normalized ratio (INR), and fibrinogen). Thus, the identified patterns suggest the numerous and diverse mechanisms of the participation of MCs and their proteases in the pathogenesis of COVID-19, and their impact on the inflammatory process and coagulation status. At the same time, the issue requires further study in larger cohorts of patients, which will open up the possibility of using drugs acting on this link of pathogenesis to treat lung damage in patients with COVID-19.

Mast Cells in the Microenvironment of Hepatocellular Carcinoma Confer Favorable Prognosis: A Retrospective Study using QuPath Image Analysis Software.

The insights provided by in-situ detection of immune cells within hepatocellular carcinoma (HCC) might present information on patient outcomes. Studies investigating the expression and localization of immune cells within tumor tissues are associated with several challenges, including a lack of precise annotation for tumor regions and random selection of microscopic fields of view. QuPath is an open-source, user-friendly software that could meet the growing need for digital pathology in whole-slide image (WSI) analysis. The infiltration of HCC and adjacent tissues by CD1a+ immature dendritic cells (iDCs), CD117+ mast cells, and NKp46+ natural killer cells (NKs) cells was assessed immunohistochemically in representative specimens of 67 patients with HCC who underwent curative resection. The area fraction (AF) of positively stained cells was assessed automatically in WSIs using QuPath in the tumor center (TC), inner margin (IM), outer margin (OM), and peritumor (PT) area. The prognostic significance of immune cells was evaluated for time to recurrence (TTR), disease-free survival (DFS), and overall survival (OS). The AF of mast cells was significantly greater than the AF of NKs, and the AF of iDCs was significantly lower compared to NKs in each region of interest. High AFs of mast cells in the IM and PT areas were associated with longer DFS. In addition, high AF of mast cells in IM was associated with longer OS. Computer-assisted analysis using this software is a suitable tool for obtaining prognostic information for tumor-infiltrating immune cells (iDCs, mast cells, and NKs) in different regions of HCC after resection. Mast cells displayed the greatest AF in all regions of interest (ROIs). Mast cells in the peritumor region and IM showed a positive prognostic significance.

High Intraepithelial Mast Cell Density in Warthin's Tumor.

BACKGROUND/AIM: Warthin's tumor, the second most frequent neoplasia of the parotid gland, is characterized by a proliferation of both epithelial and lymphoid components. In addition to epithelial and lymphoid cells, various other cell types are implicated to varying degrees in the immune response. Notably, mast cells have long been recognized as a consistent cell population within this tumor. Despite the historical acknowledgment of mast cell presence, their true distribution and significance within Warthin's tumor remain unclear. In this study, we aimed to elucidate the distribution and significance of mast cells in Warthin's tumor. MATERIALS AND METHODS: Histochemical and immunohistochemical methods were employed for the evaluation of mast cells within tumor specimens. RESULTS: Our study revealed a notable concentration of mast cells in the epithelial component of Warthin's tumor. Microscopic examination showed predominant lymphoid and epithelial elements with occasional cystic formations. Immunohistochemical analysis identified mast cells in both components, emphasizing their role in the tumor microenvironment. Double immunostaining (mast cell tryptase and CD34) revealed no significant correlation between mast cells and blood vessels. Intraepithelial mast cells (IEMCs) had a significantly higher density in the epithelial component, suggesting a potential association with the tumor's benign nature. The relationship between IEMCs and epithelial cells, especially in the presence of cystic structures, offers valuable insights into the unique features of Warthin's tumor. CONCLUSION: Our study contributes to the understanding of mast cells in Warthin's tumor, highlighting a substantial concentration within the epithelial component. This knowledge may pave the way for further investigations into the roles of mast cells in the pathogenesis and treatment of Warthin's tumor.

The Role Played by Autophagy in FcεRI-Dependent Activation of Mast Cells.

The significant role of mast cells in the development of allergic and inflammatory diseases is well-established. Among the various mechanisms of mast cell activation, the interaction of antigens/allergens with IgE and the subsequent binding of this complex to the high-affinity IgE receptor FcεRI stand out as the most studied and fundamental pathways. This activation process leads to the rapid exocytosis of granules containing preformed mediators, followed by the production of newly synthesized mediators, including a diverse array of cytokines, chemokines, arachidonic acid metabolites, and more. While conventional approaches to allergy control primarily focus on allergen avoidance and the use of antihistamines (despite their associated side effects), there is increasing interest in exploring novel methods to modulate mast cell activity in modern medicine. Recent evidence suggests a role for autophagy in mast cell activation, offering potential avenues for utilizing low-molecular-weight autophagy regulators in the treatment of allergic diseases. More specifically, mitochondria, which play an important role in the regulation of autophagy as well as mast cell activation, emerge as promising targets for drug development. This review examines the existing literature regarding the involvement of the molecular machinery associated with autophagy in FcεRI-dependent mast cell activation.