The Cytokine TGF-β Induces Interleukin-31 Expression from Dermal Dendritic Cells to Activate Sensory Neurons and Stimulate Wound Itching

Immunity. 2020 Aug 18;53(2):371-383.e5. doi: 10.1016/j.immuni.2020.06.023. Epub 2020 Jul 15.


Cutaneous wound healing is associated with the unpleasant sensation of itching. Here we investigated the mechanisms underlying this type of itch, focusing on the contribution of soluble factors released during healing. We found high amounts of interleukin 31 (IL-31) in skin wound tissue during the peak of itch responses. Il31-/- mice lacked wound-induced itch responses. IL-31 was released by dermal conventional type 2 dendritic cells (cDC2s) recruited to wounds and increased itch sensory neuron sensitivity. Transfer of cDC2s isolated from late-stage wounds into healthy skin was sufficient to induce itching in a manner dependent on IL-31 expression. Addition of the cytokine TGF-β1, which promotes wound healing, to dermal DCs in vitro was sufficient to induce Il31 expression, and Tgfbr1f/f CD11c-Cre mice exhibited reduced scratching and decreased Il31 expression in wounds in vivo. Thus, cDC2s promote itching during skin would healing via a TGF-β-IL-31 axis with implications for treatment of wound itching.

Keywords: dermal dendritic cells; interleukin-31; itch; neuro-immune interaction; transforming growth factor beta; wound healing.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Female
  • Humans
  • Interleukins / genetics
  • Interleukins / metabolism*
  • Langerhans Cells / physiology*
  • Langerhans Cells / transplantation
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Middle Aged
  • Pruritus / pathology*
  • Receptors, Interleukin / metabolism
  • Sensory Receptor Cells / physiology*
  • Skin / cytology
  • Skin / growth & development
  • Skin / injuries
  • TRPV Cation Channels / metabolism
  • Transforming Growth Factor beta1 / metabolism*
  • Wound Healing / physiology


  • Il31ra protein, mouse
  • Interleukins
  • Receptors, Interleukin
  • TRPV Cation Channels
  • TRPV1 protein, mouse
  • Tgfb1 protein, mouse
  • Transforming Growth Factor beta1
  • interleukin-31, mouse