Differential Roles of interleukin-17A and -17F in Host Defense Against Mucoepithelial Bacterial Infection and Allergic Responses

Immunity. 2009 Jan 16;30(1):108-19. doi: 10.1016/j.immuni.2008.11.009.

Abstract

Interleukin-17A (IL-17A) is a cytokine produced by T helper 17 (Th17) cells and plays important roles in the development of inflammatory diseases. Although IL-17F is highly homologous to IL-17A and binds the same receptor, the functional roles of this molecule remain largely unknown. Here, we demonstrated with Il17a(-/-), Il17f(-/-), and Il17a(-/-)Il17f(-/-) mice that IL-17F played only marginal roles, if at all, in the development of delayed-type and contact hypersensitivities, autoimmune encephalomyelitis, collagen-induced arthritis, and arthritis in Il1rn(-/-) mice. In contrast, both IL-17F and IL-17A were involved in host defense against mucoepithelial infection by Staphylococcus aureus and Citrobacter rodentium. IL-17A was produced mainly in T cells, whereas IL-17F was produced in T cells, innate immune cells, and epithelial cells. Although only IL-17A efficiently induced cytokines in macrophages, both cytokines activated epithelial innate immune responses. These observations indicate that IL-17A and IL-17F have overlapping yet distinct roles in host immune and defense mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis / genetics
  • Arthritis / immunology*
  • Bacterial Infections / immunology*
  • Bacterial Infections / prevention & control
  • Cells, Cultured
  • Cytokines / metabolism*
  • Flow Cytometry
  • Hypersensitivity / immunology*
  • Interleukin-17 / classification*
  • Interleukin-17 / genetics
  • Interleukin-17 / physiology*
  • Mice
  • Mice, Knockout

Substances

  • Cytokines
  • Interleukin-17