A novel subset of CD4(+) T(H)2 memory/effector cells that produce inflammatory IL-17 cytokine and promote the exacerbation of chronic allergic asthma

J Exp Med. 2010 Oct 25;207(11):2479-91. doi: 10.1084/jem.20101376. Epub 2010 Oct 4.

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 T(H)2 memory/effector cells that coexpress the transcription factors GATA3 and RORγt 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-1β, 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Asthma / immunology*
  • Asthma / metabolism
  • Asthma / pathology
  • Chronic Disease
  • Cytokines / biosynthesis
  • Cytokines / immunology
  • GATA3 Transcription Factor / biosynthesis
  • GATA3 Transcription Factor / immunology
  • Gene Expression Regulation / immunology
  • Humans
  • Immunologic Memory*
  • Interleukin-17 / biosynthesis
  • Interleukin-17 / immunology*
  • Lymphocyte Subsets / immunology*
  • Lymphocyte Subsets / metabolism
  • Lymphocyte Subsets / pathology
  • Mice
  • Mice, Inbred BALB C
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / biosynthesis
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / immunology
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism
  • Th2 Cells / pathology

Substances

  • Cytokines
  • GATA3 Transcription Factor
  • GATA3 protein, human
  • Interleukin-17
  • Nuclear Receptor Subfamily 1, Group F, Member 3