Regulation of selective class switching provides long-term therapeutic benefits for hay fever
IgA protects the body from invaders in the mucosal sites, but its role in allergic diseases, such as hay fever, is poorly understood. We demonstrate an increased susceptibility to cedar-pollen-induced hay fever associated with increasing pollen penetration into the body in IgA-deficient mice, indicating that IgA prevents pollen invasion in the mucosa. We identified bryostatin 1, an anticarcinogenic protein kinase Cδ (PKCδ) activator, as an IgA/IgE class-switching regulator in B cells. Bryostatin 1 enhanced IgA production through induction of germline transcript α (GLTα) via the PKCδ/MEK/ERK/RUNX1 pathway and suppressed IgE by reducing GLTε through the PKCδ/STAT5/ID2 pathway. Production of Th2 cytokines and eosinophil infiltration in the lungs was also reduced. Furthermore, hay fever alleviation by bryostatin 1 demonstrated diminished symptoms in mice in vivo 3 months subsequent to intranasal administration.
Authors
- Tianxiang Huang (ORCID: https://orcid.org/0000-0001-8867-1367)
- Reiko Shinkura (ORCID: https://orcid.org/0000-0002-7976-9933)
- Takenori Inomata
- Takahiro Nagatake (ORCID: https://orcid.org/0000-0003-3022-9626)
- Manabu Sugai (ORCID: https://orcid.org/0000-0003-1668-7647)
- Hirotatsu Kojima (ORCID: https://orcid.org/0000-0002-5480-3189)
- Peng Gao (ORCID: https://orcid.org/0000-0002-9991-6064)
- Takahiro Adachi (ORCID: https://orcid.org/0000-0002-3711-8577)
- Kiyoko Yamamoto
- Keiichi I. Nakayama
- Yasuhiro Yamada
- Naoki Morita
- Ryutaro Tamano
Institutions
- University of Fukui (JP)
- Fukui University of Technology (JP)
- Tokyo Medical and Dental University (JP)
- Meiji University (JP)
- Juntendo University (JP)
- Laboratory of Molecular Genetics (PL)
- National Institute of Hospital Administration (CN)
- Quantitative BioSciences (US)
- Frontier Science Foundation (CH)
- Department of Administration (GU)
- Drug Discovery Laboratory (Norway) (NO)
- The University of Tokyo (JP)
- Nara Institute of Science and Technology (JP)
Publication Details
- Journal
- JCI Insight
- Published
- 2025-10-21
- DOI
- https://doi.org/10.1172/jci.insight.190240
- Citations
- 1
- Primary Topic
- Vector-borne infectious diseases
- Type
- article
- Field-Weighted Citation Impact
- 2.05
Funders
- Uehara Memorial Foundation
- Japan Agency for Medical Research and Development
- University of Tokyo
- Hoyu Science Foundation
- Japan Society for the Promotion of Science