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

作者：Wang, Yui-Hsi^*; Voo, Kui Shin; Liu, Bo; Chen, Chun-Yu; Uygungil, Burcin; Spoede, William; Bernstein, Jonathan A.; Huston, David P.; Liu, Yong-Jun

来源：Journal of Experimental Medicine, 2010, 207(11): 2479-2491.

DOI：10.1084/jem.20101376

• GROWTH-FACTOR-BETA
• INTERFERON-REGULATORY FACTOR-4
• COLONY-STIMULATING FACTOR
• ROR-GAMMA-T
• PROINFLAMMATORY CYTOKINES
• TGF-BETA
• AUTOIMMUNE INFLAMMATION
• NEUTROPHIL RECRUITMENT
• MOUSE MODEL
• TH2 CELLS

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(H)2 memory/effector cells that coexpress the transcription factors GATA3 and ROR gamma t and coproduce T(H)17 and T(H)2 cytokines. Classical T(H)2 memory/effector cells had the potential to produce IL-17 after stimulation with proinflammatory cytokines IL-1 beta, IL-6, and IL-21. The number of IL-17-T(H)2 cells was significantly increased in blood of patients with atopic asthma. In a mouse model of allergic lung diseases, IL-17-producing CD4(+) T(H)2 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(H)2 cytokines induced strong up-regulation of chemokine eotaxin-3, Il8, Mip1b, and Groa gene expression. Compared with classical T(H)17 and T(H)2 cells, antigen-specific IL-17-producing T(H)2 cells induced a profound influx of heterogeneous inflammatory leukocytes and exacerbated asthma. Our findings highlight the plasticity of T(H)2 memory cells and suggest that IL-17-producing T(H)2 cells may represent the key pathogenic T(H)2 cells promoting the exacerbation of allergic asthma.

• 出版日期2010-10-25