A novel subset of CD4⁺ T_H2 memory/ effector cells that produce inflammatory IL-17 cytokine and promote the exacerbation of chronic allergic asthma

The inflammatory cytokine interleukin (IL)-17 is involved in the pathogenesis of allergic diseases. However, the identity and functions of IL-17-producing T cells during the pathogenesis of allergic diseases remain unclear. Here, we report a novel subset of T_H2 memory/ effector cells that coexpress the transcription factors GATA3 and RORγt and coproduce T_H17 and T_H2 cytokines. Classical T_H2 memory/effector cells had the potential to produce IL-17 after stimulation with proinflammatory cytokines IL-1β, IL-6, and IL-21. The number of IL-17-T_H2 cells was significantly increased in blood of patients with atopic asthma. In a mouse model of allergic lung diseases, IL-17-producing CD4⁺ T_H2 cells were induced in the inflamed lung and persisted as the dominant IL-17-producing T cell population during the chronic stage of asthma. Treating cultured bronchial epithelial cells with IL-17 plus T_H2 cytokines induced strong up-regulation of chemokine eotaxin-3, Il8, Mip1b, and Groa gene expression. Compared with classical T_H17 and T_H2 cells, antigen-specific IL-17-producing T_H2 cells induced a profound influx of heterogeneous inflammatory leukocytes and exacerbated asthma. Our findings highlight the plasticity of T_H2 memory cells and suggest that IL-17-producing TH2 cells may represent the key pathogenic T_H2 cells promoting the exacerbation of allergic asthma.