Chronic urticaria and the pathogenic role of mast cells

Elieh‐Ali‐Komi, Daniel; Metz, Martin; Kolkhir, Pavel; Kocatürk, Emek; Frischbutter, Stefan; Terhorst‐Molawi, Dorothea; Fox, Lena; Maurer, Marcus

doi:10.1016/j.alit.2023.05.003

Cited by 34 publications

(12 citation statements)

References 143 publications

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“…Finally, there are several knowledge gaps in our understanding of MC participation in the pathogenesis of parasympathetic paraganglioma and shaping its TME: (a) MCs produce MMPs mainly MMP‐9, which play a key role in ECM degradation and are implicated in cancer invasion and metastases. Investigation of MC production of MMPs could be an interesting research theme, (b) possible association of MC subtypes or their dominancy to prognosis is still poorly described, (c) silencing or depleting MCs was not possible until the introduction of lirentelimab (binds to inhibitory receptor Siglec‐8) and barzolvolimab (also known as CDX‐0159, binds c‐KIT and its dimerization) respectively (Elieh‐Ali‐Komi et al, 2023). Considering the tumorogenic activity of MCs in some tumor types, that may be worth investigating their role after silencing or depleting them.…”

Section: Discussionmentioning

confidence: 99%

Ultrastructural features of tumor‐associated mast cells in parasympathetic paragangliomas (chemodectomas) of the neck

Chekmaryova,

Kalinin,

Kostin

et al. 2024

Microscopy Res & Technique

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The mechanisms of the pathogenesis of neck paraganglioma (PGL) and the possible role of mast cells (MCs) in its development and metastasis are still poorly understood. We analyzed MCs' morphologic characterization, activation, and the properties of their cytoplasmic/released granules in PGLs, using light and transmission electron microscopy. Paragangliomas showed a large tumor‐associated MC population both in the connective tissue layers of the tumor and between the tumor cells. Notably, MCs were presented by a high expression of specific proteases, size variation, polymorphism, and variable ultrastructural phenotype of granules. A massive number of granules were released surrounding the degranulated MCs while the integrity of MC membrane was maintained. Granules were electron‐dense with or without a membrane, ranging from 0.2 to 0.8 μm in diameter. MC plasmalemma was not found at the site of MC‐collagen fibrils contact, whereas the secretome and fibrils were directly contacted. We observed direct and mediator‐based interactions between MCs and paraganglioma cells. The latter preserved their membrane integrity when MC granules were not in proximity. The effects of the MC secretome on the paraganglioma microenvironment demonstrated its pathogenetic role in tumor progression and allow its application to new diagnostic criteria and the development of protocols for personalized therapy.Research Highlights Ultrastructural analysis reveals novel regulatory effects of mast cells via diverse secretory pathways on the pathogenesis of parasympathetic paraganglioma, including fibrous extracellular matrix remodeling and mediator‐based interactions between MCs and cells of the tumor microenvironment.

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Section: Discussionmentioning

confidence: 99%

Ultrastructural features of tumor‐associated mast cells in parasympathetic paragangliomas (chemodectomas) of the neck

Chekmaryova,

Kalinin,

Kostin

et al. 2024

Microscopy Res & Technique

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“…TNF‐alpha can influence blood vessels by promoting vasodilation and increasing permeability of blood vessels. 23 In CU, the effects of TNF‐alpha on blood vessels lead to increased permeability, allowing fluid to leak from blood vessels into the surrounding tissue. This fluid leakage contributes to edema and redness commonly observed in hives or urticarial lesions.…”

Section: Discussionmentioning

confidence: 99%

Identification of key genes and molecular mechanisms of chronic urticaria based on bioinformatics

Guo,

et al. 2024

Skin Research and Technology

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Chronic urticaria (CU) is characterized by persistent skin hives, redness, and itching, enhanced by immune dysregulation and inflammation. Our main objective is identifying key genes and molecular mechanisms of chronic urticaria based on bioinformatics. We used the Gene Expression Omnibus (GEO) database and retrieved two GEO datasets, GSE57178 and GSE72540. The raw data were extracted, pre‐processed, and analyzed using the GEO2R tool to identify the differentially expressed genes (DEGs). The samples were divided into two groups: healthy samples and CU samples. We defined cut‐off values of log2 fold change ≥1 and p < .05. Analyses were performed in the Kyoto Encyclopaedia of Genes and Genomes (KEGG), the Database for Annotation, Visualization and Integrated Discovery (DAVID), Metascape, Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and CIBERSOFT databases. We obtained 1613 differentially expressed genes. There were 114 overlapping genes in both datasets, out of which 102 genes were up‐regulated while 12 were down‐regulated. The biological processes included activation of myeloid leukocytes, response to inflammations, and response to organic substances. Moreover, the KEGG pathways of CU were enriched in the Nuclear Factor‐Kappa B (NF‐kB) signaling pathway, Tumor Necrosis Factor (TNF) signaling pathway, and Janus kinase/signal transducers and activators of transcription (JAK‐STAT) signaling pathway. We identified 27 hub genes that were implicated in the pathogenesis of CU, such as interleukin‐6 (IL‐6), Prostaglandin‐endoperoxide synthase 2 (PTGS2), and intercellular adhesion molecule‐1 (ICAM1). The complex interplay between immune responses, inflammatory pathways, cytokine networks, and specific genes enhances CU. Understanding these mechanisms paves the way for potential interventions to mitigate symptoms and improve the quality of life of CU patients.

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“…Notably, the activation of Mas-related G protein-coupled receptor X2 (MRGPRX2) is observed in the skin MCs of patients suffering from CSU. Other pathways contributing to MC activation in CSU involve IL-33, ST2, and thymic stromal lymphopoietin (TSLP) [ 95 ]. It has been demonstrated that the amounts of IL-25, IL-33, and TSLP are elevated in the affected skin of patients with CSU, indicating the potential involvement of ILC2s in the pathological processes of CSU [ 96 ].…”

Section: Cross-talk Between Skin Mcs and Ilc2smentioning

confidence: 99%

Communication between Mast Cells and Group 2 Innate Lymphoid Cells in the Skin

Mehrani,

Morovati,

Tajik

et al. 2024

Cells

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The skin is a dynamic organ with a complex immune network critical for maintaining balance and defending against various pathogens. Different types of cells in the skin, such as mast cells (MCs) and group 2 innate lymphoid cells (ILC2s), contribute to immune regulation and play essential roles in the early immune response to various triggers, including allergens. It is beneficial to dissect cell-to-cell interactions in the skin to elucidate the mechanisms underlying skin immunity. The current manuscript concentrates explicitly on the communication pathways between MCs and ILC2s in the skin, highlighting their ability to regulate immune responses, inflammation, and tissue repair. Furthermore, it discusses how the interactions between MCs and ILC2s play a crucial role in various skin conditions, such as autoimmune diseases, dermatological disorders, and allergic reactions. Understanding the complex interactions between MCs and ILC2s in different skin conditions is crucial to developing targeted treatments for related disorders. The discovery of shared pathways could pave the way for novel therapeutic interventions to restore immunological balance in diseased skin tissues.

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Chronic urticaria and the pathogenic role of mast cells

Cited by 34 publications

References 143 publications

Ultrastructural features of tumor‐associated mast cells in parasympathetic paragangliomas (chemodectomas) of the neck

Ultrastructural features of tumor‐associated mast cells in parasympathetic paragangliomas (chemodectomas) of the neck

Identification of key genes and molecular mechanisms of chronic urticaria based on bioinformatics

Communication between Mast Cells and Group 2 Innate Lymphoid Cells in the Skin

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