A novel subset of CD4+ TH2 memory/effector cells that produce inflammatory IL-17 cytokine and promote the exacerbation of chronic allergic asthma

YH Wang, KS Voo, B Liu, CY Chen… - Journal of Experimental …, 2010 - rupress.org
YH Wang, KS Voo, B Liu, CY Chen, B Uygungil, W Spoede, JA Bernstein, DP Huston, YJ Liu
Journal of Experimental Medicine, 2010rupress.org
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 TH2
memory/effector cells that coexpress the transcription factors GATA3 and RORγt and
coproduce TH17 and TH2 cytokines. Classical TH2 memory/effector cells had the potential
to produce IL-17 after stimulation with proinflammatory cytokines IL-1β, IL-6, and IL-21. The …
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 TH2 memory/effector cells that coexpress the transcription factors GATA3 and RORγt and coproduce TH17 and TH2 cytokines. Classical TH2 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-TH2 cells was significantly increased in blood of patients with atopic asthma. In a mouse model of allergic lung diseases, IL-17–producing CD4+ TH2 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 TH2 cytokines induced strong up-regulation of chemokine eotaxin-3, Il8, Mip1b, and Groa gene expression. Compared with classical TH17 and TH2 cells, antigen-specific IL-17–producing TH2 cells induced a profound influx of heterogeneous inflammatory leukocytes and exacerbated asthma. Our findings highlight the plasticity of TH2 memory cells and suggest that IL-17–producing TH2 cells may represent the key pathogenic TH2 cells promoting the exacerbation of allergic asthma.
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