Transforming growth factor-β induces development of the T H17 lineage

Academic Article

Abstract

  • A new lineage of effector CD4 T cells characterized by production of interleukin (IL)-17, the T-helper-17 (T 17) lineage, was recently described based on developmental and functional features distinct from those of classical T 1 and T 2 lineages . Like T 1 and T 2, T 17 cells almost certainly evolved to provide adaptive immunity tailored to specific classes of pathogens , such as extracellular bacteria . Aberrant T 17 responses have been implicated in a growing list of autoimmune disorders . T 17 development has been linked to IL-23, an IL-12 cytokine family member that shares with IL-12 a common subunit, IL-12p40 (ref. 8). The IL-23 and IL-12 receptors also share a subunit, IL-12Rβ1, that pairs with unique, inducible components, IL-23R and IL-12Rβ2, to confer receptor responsiveness . Here we identify transforming growth factor-β (TGF-β) as a cytokine critical for commitment to T 17 development. TGF-β acts to upregulate IL-23R expression, thereby conferring responsiveness to IL-23. Although dispensable for the development of IL-17-producing T cells in vitro and in vivo, IL-23 is required for host protection against a bacterial pathogen, Citrobacter rodentium. The action of TGF-β on naive T cells is antagonized by interferon-γ and IL-4, thus providing a mechanism for divergence of the T 1, T 2 and T 17 lineages. © 2006 Nature Publishing Group. + 1,2 3 4 5-7 9 H H H H H H H H H H H H
  • Published In

  • Nature  Journal
  • Digital Object Identifier (doi)

    Author List

  • Mangan PR; Harrington LE; O'Quinn DB; Helms WS; Bullard DC; Elson CO; Hatton RD; Wahl SM; Schoeb TR; Weaver CT
  • Start Page

  • 231
  • End Page

  • 234
  • Volume

  • 441
  • Issue

  • 7090