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IRF3 Activation in Mast Cells Promotes FcεRI-Mediated Allergic Inflammation

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Author(s)
Young-Ae ChoiHima DhakalSoyoung LeeNamkyung KimByungheon LeeTaeg Kyu KwonDongwoo KhangSang-Hyun Kim
Keimyung Author(s)
Kwon, Taeg Kyu
Department
Dept. of Immunology (면역학)
Journal Title
Cells
Issued Date
2023
Volume
12
Issue
11
Keyword
allergic inflammationhistaminehistidine decarboxylaseinterferon regulatory factor 3mast cells
Abstract
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.

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.

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.

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.
Keimyung Author(s)(Kor)
권택규
Publisher
School of Medicine (의과대학)
Type
Article
ISSN
2073-4409
Source
https://www.mdpi.com/2073-4409/12/11/1493
DOI
10.3390/cells12111493
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/44960
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
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