Regulatory T Cells Restrain Pathogenic T Helper Cells during Skin Inflammation

Cell Rep. 2018 Dec 26;25(13):3564-3572.e4. doi: 10.1016/j.celrep.2018.12.012.


Psoriasis is a chronic relapsing, remitting interleukin (IL)-23/IL-17-driven skin disease mediated by the interplay of T cells and polymorphonuclear granulocytes. Although preclinical studies have provided insights into the mechanisms of disease initiation, the underpinnings of natural disease remission remain largely unknown. Here, we addressed the contribution of regulatory Foxp3+ T cells (Treg cells) in psoriasiform skin inflammation and remission using the Aldara-skin inflammation model in combination with the inducible depletion of Foxp3+ Treg cells. Loss of Treg cells exacerbated skin inflammation, but this did not involve increased γδ T cell expansion or the local production of the psoriasis-associated cytokines IL-17A, IL-17F, and IL-22, which are the main driving forces of disease development. Instead, Treg cells suppressed the infiltration of granulocyte-macrophage colony-stimulating factor (GM-CSF)-producing CD4+ T cells into the lesioned skin, and neutralizing GM-CSF in Treg cell-deficient mice reversed hyper-inflammation, resulting in disease regression. Therefore, we identified a non-redundant role of Treg cells restraining skin inflammation and mediating skin homeostasis.

Keywords: Aldara; CD4 T cells; Foxp3; GM-CSF; Treg cells; ipilimumab; melanoma; psoriasis; skin inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Female
  • Forkhead Transcription Factors / metabolism
  • Granulocyte-Macrophage Colony-Stimulating Factor / biosynthesis
  • Humans
  • Imiquimod / adverse effects
  • Inflammation / chemically induced
  • Inflammation / immunology*
  • Inflammation / pathology
  • Male
  • Mice, Inbred C57BL
  • Middle Aged
  • Neutralization Tests
  • Phagocytes / pathology
  • Psoriasis / immunology
  • Psoriasis / pathology
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism
  • Skin / pathology*
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Regulatory / immunology*


  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Receptors, Antigen, T-Cell, alpha-beta
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Imiquimod