IL-23 induced in keratinocytes by endogenous TLR4 ligands polarizes dendritic cells to drive IL-22 responses to skin immunization Academic Article uri icon


MeSH Major

  • Cell Polarity
  • Dendritic Cells
  • Immunization
  • Interleukin-23
  • Interleukins
  • Keratinocytes
  • Skin
  • Toll-Like Receptor 4


  • Atopic dermatitis (AD) is a Th2-dominated inflammatory skin disease characterized by epidermal thickening. Serum levels of IL-22, a cytokine known to induce keratinocyte proliferation, are elevated in AD, and Th22 cells infiltrate AD skin lesions. We show that application of antigen to mouse skin subjected to tape stripping, a surrogate for scratching, induces an IL-22 response that drives epidermal hyperplasia and keratinocyte proliferation in a mouse model of skin inflammation that shares many features of AD. DC-derived IL-23 is known to act on CD4(+) T cells to induce IL-22 production. However, the mechanisms that drive IL-23 production by skin DCs in response to cutaneous sensitization are not well understood. We demonstrate that IL-23 released by keratinocytes in response to endogenous TLR4 ligands causes skin DCs, which selectively express IL-23R, to up-regulate their endogenous IL-23 production and drive an IL-22 response in naive CD4(+) T cells that mediates epidermal thickening. We also show that IL-23 is released in human skin after scratching and polarizes human skin DCs to drive an IL-22 response, supporting the utility of IL-23 and IL-22 blockade in AD.

publication date

  • January 2016



  • Academic Article



  • eng

PubMed Central ID

  • PMC5032726

Digital Object Identifier (DOI)

  • 10.1084/jem.20150376

PubMed ID

  • 27551155

Additional Document Info

start page

  • 2147

end page

  • 66


  • 213


  • 10