Th2 cells and macrophages induce novel type-I-hypersensitivity-like reaction

Abstract

In recent decades, many patients have been suffering from allergic rhinitis including Japanese cedar pollinosis, which is becoming a national disease in Japan. There is other upper airway intractable disease, called eosinophilic sinusitis. The elucidation of the pathogenesis of upper airway intractable disease is demanded for the development of novel therapies. Many researches about allergic pathogenesis have focused on IgE-mast cells pathway, however, there are the patients with allergic symptoms induced by non-IgE mediated mechanisms. The patients who show allergic rhinitis-like symptoms, such as sneezing, nasal discharge, and nasal clotting, without allergen-specific IgE, are diagnosed as non-allergic rhinitis. The precise mechanisms of non-allergic rhinitis are totally unclear. We have investigated the non-IgE mediated nasal symptoms, because the elucidation of non-IgE mediated mechanisms might lead to the elucidation of other upper airway intractable disease. We established antigen-specific Th2 cells transfer model and revealed the novel allergic mechanisms induced by Th2 cells, macrophages and endotoxin. Although Th2 cells play important roles in allergic diseases, the main function of Th2 cells are thought to produce Th2 cytokines, such as interleukin (IL)-4, IL-5, IL-13. We revealed the new functions of Th2 cells in allergic diseases. In addition, we found the novel histamine production mechanisms using in vitro macrophages and Th2 cells co-culture model. Both macrophages and Th2 cells produced histamine by the interaction through antigen. Our observations suggested the existence of the novel allergic mechanisms distinct from IgE-mast cells pathway.