ArticleCells2021
Thymic Stromal Lymphopoietin Promotes MRGPRX2-Triggered Degranulation of Skin Mast Cells in a STAT5-Dependent Manner with Further Support from JNK.
Article in Cells, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 41 citations in OpenAlex.
- Rewiring Atopic Dermatitis: Alarmin Cytokines at the Core of Barrier-Immune-Neuro-Microbiome Networks.Clinical reviews in allergy & immunology · 2026Review
- Successful Application of the Mast Cell Activation Test in Immediate Hypersensitivity to Amoxicillin.Allergy · 2026Article
- Immunosenescence and Allergy: Molecular and Cellular Links Between Inflammaging, Neuro-Immune Aging, and Response to Biologic Therapies.International journal of molecular sciences · 2026Review
- Therapeutic effect of an MRGPRX2/MRGPRB2 antagonist on LL-37-induced rosacea-like inflammation in mice.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- Icatibant Acts as a Balanced Ligand of MRGPRX2 in Human Skin Mast Cells.Biomolecules · 2025Article
- Transcriptional Regulation of Mouse Mast Cell Differentiation and the Role of Human Lung Mast Cells in Airway Inflammation.Immunological reviews · 2025Review
- Neurogenic Inflammation in Allergic Contact Dermatitis.Biomedicines · 2025Review
- Beyond the classic players: Mas-related G protein-coupled receptor member X2 role in pruritus and skin diseases.Journal of the European Academy of Dermatology and Venereology : JEADV · 2025Review
- Mast Cells at the Crossroads of Hypersensitivity Reactions and Neurogenic Inflammation.International journal of molecular sciences · 2025Review
- TSLP: contrasting roles in cancer.Frontiers in immunology · 2025Review
- Characterization of Freshly Isolated Human Peripheral Blood B Cells, Monocytes, CD4+ and CD8+ T Cells, and Skin Mast Cells by Quantitative Transcriptomics.International journal of molecular sciences · 2024Article
- CREB Is Critically Implicated in Skin Mast Cell Degranulation Elicited via FcεRI and MRGPRX2.Cells · 2024Article
- Comparative analyses of various IgE-mediated and non-IgE-mediated inducers of mast cell degranulation for in vitro study.Immunologic research · 2024Article
- MRGPRX2 antagonist GE1111 attenuated DNFB-induced atopic dermatitis in mice by reducing inflammatory cytokines and restoring skin integrity.Frontiers in immunology · 2024Article
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- CREB Is Activated by the SCF/KIT Axis in a Partially ERK-Dependent Manner and Orchestrates Survival and the Induction of Immediate Early Genes in Human Skin Mast Cells.International journal of molecular sciences · 2023Article
- Activation of ryanodine-sensitive calcium store drives pseudo-allergic dermatitisFrontiers in immunology · 2023Article
- The Role of TSLP in Atopic Dermatitis: From Pathogenetic Molecule to Therapeutical Target.Mediators of inflammation · 2023Review
- How "Neuronal" Are Human Skin Mast Cells?International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Thymic stromal lymphopoietin (TSLP) is released by epithelial cells following disturbed homeostasis to act as "alarmin" and driver of Th2-immunity. Aberrant TSLP expression is a hallmark of atopic diseases, including atopic dermatitis (AD). Mast cells (MCs) are overabundant in AD lesions and show signs of degranulation, but it remains unknown whether TSLP contributes to granule discharge. Degranulation of skin MCs proceeds via two major routes, i.e., FcεRI-dependent (allergic) and MRGPRX2-mediated (pseudo-allergic/neurogenic). Evidence is accumulating that MRGPRX2 may be crucial in the context of skin diseases, including eczema. The current study reveals TSLP as a novel priming factor of human skin MCs. Interestingly, TSLP selectively cooperates with MRGPRX2 to support granule discharge, while it does not impact spontaneous or FcεRI-driven exocytosis. TSLP-assisted histamine liberation triggered by compound 48/80 or Substance P, two canonical MRGPRX2 agonists, was accompanied by an increase in CD107a+ cells (a MC activation marker). The latter process was less potent, however, and detectable only at the later of two time points, suggesting TSLP may prolong opening of the granules. Mechanistically, TSLP elicited phosphorylation of STAT5 and JNK in skin MCs and the reinforced degranulation critically depended on STAT5 activity, while JNK had a contributory role. Results from pharmacological inhibition were confirmed by RNA-interference, whereby silencing of STAT5 completely abolished the priming effect of TSLP on MRGPRX2-mediated degranulation. Collectively, TSLP is the first factor to favor MRGPRX2- over FcεRI-triggered MC activation. The relevance of TSLP, MCs and MRGPRX2 to pruritis and atopic skin pathology indicates broad repercussions of the identified connection.
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