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IRF3 Activation in Mast Cells Promotes FcεRI-Mediated Allergic Inflammation.
- Source :
- Cells (2073-4409); Jun2023, Vol. 12 Issue 11, p1493, 15p
- Publication Year :
- 2023
-
Abstract
- (1) Background: This study aims to elucidate a novel non-transcriptional action of IRF3 in addition to its role as a transcription factor in mast cell activation and associated allergic inflammation; (2) Methods: For in vitro experiments, mouse bone-marrow-derived mast cells (mBMMCs) and a rat basophilic leukemia cell line (RBL-2H3) were used for investigating the underlying mechanism of IRF3 in mast-cell-mediated allergic inflammation. For in vivo experiments, wild-type and Irf3 knockout mice were used for evaluating IgE-mediated local and systemic anaphylaxis; (3) Results: Passive cutaneous anaphylaxis (PCA)-induced tissues showed highly increased IRF3 activity. In addition, the activation of IRF3 was observed in DNP-HSA-treated mast cells. Phosphorylated IRF3 by DNP-HSA was spatially co-localized with tryptase according to the mast cell activation process, and FcεRI-mediated signaling pathways directly regulated that activity. The alteration of IRF3 affected the production of granule contents in the mast cells and the anaphylaxis responses, including PCA- and ovalbumin-induced active systemic anaphylaxis. Furthermore, IRF3 influenced the post-translational processing of histidine decarboxylase (HDC), which is required for granule maturation; and (4) Conclusion: Through this study, we demonstrated the novel function of IRF3 as an important factor inducing mast cell activation and as an upstream molecule for HDC activity. [ABSTRACT FROM AUTHOR]
- Subjects :
- MAST cells
TRYPTASE
KNOCKOUT mice
INTERFERON regulatory factors
Subjects
Details
- Language :
- English
- ISSN :
- 20734409
- Volume :
- 12
- Issue :
- 11
- Database :
- Complementary Index
- Journal :
- Cells (2073-4409)
- Publication Type :
- Academic Journal
- Accession number :
- 164214188
- Full Text :
- https://doi.org/10.3390/cells12111493