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

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

Research output: Contribution to journalArticle

298 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2479-2491
Number of pages13
JournalJournal of Experimental Medicine
Volume207
Issue number11
DOIs
StatePublished - Oct 25 2010

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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