Mast cells promote inflammatory Th17 cells and impair Treg cells through an IL-1β and PGE2 axis
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Author(s)
Type
Journal Article
Abstract
Purpose: CD4+ effector T cells (Teffs) play a key role in immune responses by infiltrating the sites of inflammation and modulating local leukocyte activity. In turn resident immune cells shape their response. This study aimed to investigate the influence of mast cells (MCs) on Teff biological responses.
Methods: This study examined human MC-Teff interactions, focusing on how MCs shape Teff responses. Flow cytometry, qRT-PCR, and cytokine assays were used to analyze the impact of primary human MCs on the Teff phenotype and function. MC-Teff crosstalk within Crohn’s disease patient tissues was assessed using confocal microscopy and advanced image analysis.
Results: MCs promoted the differentiation of Th17 cells, particularly the inflammatory Th17.1 subset, that secretes IFN-γ and GM-CSF. This differentiation was driven by the PGE2 and IL-1β axis. Additionally, MCs disrupted the phenotype and impaired the suppressive function of regulatory T cells (Tregs) through PGE2, skewing the Th17/Treg balance. The analysis of biopsies from patients with Crohn’s disease indicated that this MC/Teff crosstalk may play a role in the pathogenesis of auto-inflammatory processes.
Conclusion: MCs influence CD4+ T cell responses by fostering pro-inflammatory Th17 differentiation while impairing Treg function. This interaction underpins a Th17/Treg imbalance, which is significant in auto-inflammatory diseases such as Crohn’s disease, positioning MCs as critical drivers of disease pathogenesis.
Methods: This study examined human MC-Teff interactions, focusing on how MCs shape Teff responses. Flow cytometry, qRT-PCR, and cytokine assays were used to analyze the impact of primary human MCs on the Teff phenotype and function. MC-Teff crosstalk within Crohn’s disease patient tissues was assessed using confocal microscopy and advanced image analysis.
Results: MCs promoted the differentiation of Th17 cells, particularly the inflammatory Th17.1 subset, that secretes IFN-γ and GM-CSF. This differentiation was driven by the PGE2 and IL-1β axis. Additionally, MCs disrupted the phenotype and impaired the suppressive function of regulatory T cells (Tregs) through PGE2, skewing the Th17/Treg balance. The analysis of biopsies from patients with Crohn’s disease indicated that this MC/Teff crosstalk may play a role in the pathogenesis of auto-inflammatory processes.
Conclusion: MCs influence CD4+ T cell responses by fostering pro-inflammatory Th17 differentiation while impairing Treg function. This interaction underpins a Th17/Treg imbalance, which is significant in auto-inflammatory diseases such as Crohn’s disease, positioning MCs as critical drivers of disease pathogenesis.
Date Issued
2025-04-30
Date Acceptance
2025-04-10
Citation
Journal of Inflammation Research, 2025, 18, pp.5851-5865
ISSN
1178-7031
Publisher
Dove Medical Press
Start Page
5851
End Page
5865
Journal / Book Title
Journal of Inflammation Research
Volume
18
Copyright Statement
© 2025 Leveque et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms. php and incorporate the Creative Commons Attribution – Non Commercial (unported, v4.0) License (http://creativecommons.org/licenses/by-nc/4.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
License URL
Identifier
10.2147/JIR.S509931
Subjects
mast cells
helper T cells
prostaglandin E2
IL-1β
Th17
inflammatory Th17.1 cells
Crohn disease
IL-17
IFN-γ
Publication Status
Published
Date Publish Online
2025-04-30