IL-1 and Innate Immunity in the Differentiation of TH17 Cells

  • Stephen J. Lalor
  • Caroline E. Sutton
  • Kingston H. G. Mills


CD4+ T cells that secrete IL-17 (TH17 cells) play a key role in the pathogenesis of many auto-immune diseases and function with TH1 cells to mediate protective immunity to pathogens. The differentiation and expansion of TH17 cells from naïve T cells appears to involve signals from IL-6, IL-1 IL-21, and IL-23. The role of TGF-β is more controversial with evidence that it can promote differentiation but also inhibit activation of TH17 cells. Although much of the focus has been on CD4+ T cells, and more recently CD8+ T cells, there is increasing evidence that innate cells, especially γδ T cells, but also NKT cells, are important sources of IL-17 and other TH17 associated cytokines. We have found that IL-1α or IL-1β can synergize with IL-23 to promote IL-17 secretion from memory T cells, and that IL-1β and IL-23, produced by dendritic cells in response to Toll-like receptor and NOD-like receptor activation, can also promote IL-17 production by γδ T cells without T cell receptor engagement. IL-17-producing γδ T cells are found at high frequency in the brain and spinal cord of mice with experimental auto-immune encephalomyelitis, where they function with TH17 cells to mediate auto-immune inflammation and pathology. γδ T cells appear to act as an important source of innate IL-17 and IL-21, which act in an amplification loop early in the immune response to promote further IL-17 production by TH17 cells. This chapter discusses the role of IL-1 and IL-23 in promoting IL-17 production by antigen-specific TH17 cells and innate IL-17 from γδ T cells and the role of IL-17-producing γδ T cells in auto-immunity and infection.


Multiple Sclerosis TH17 Cell Treg Cell Innate Immune Cell Anthrax Lethal Toxin 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Stephen J. Lalor
  • Caroline E. Sutton
  • Kingston H. G. Mills
    • 1
  1. 1.School of Biochemistry and ImmunologyTrinity College DublinDublin 2Ireland

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