Abstract
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
Naoki Morita, Kohta Yamamoto, Ryutaro Tamano, Peng Gao, Takahiro Nagatake, Takenori Inomata, Tianxiang Huang, Yasuhiro Yamada, Takahiro Adachi, Manabu Sugai, Keiichi I. Nakayama, Hirotatsu Kojima, Reiko Shinkura
Graphical abstract
