IL-23 from Langerhans cells is required for the development of imiquimod-induced psoriasis-like dermatitis by induction of IL-17A-producing γδ T cells

J Invest Dermatol. 2014 Jul;134(7):1912-1921. doi: 10.1038/jid.2014.98. Epub 2014 Feb 25.

Abstract

Psoriasis is a common chronic inflammatory skin disease that involves dysregulated interplay between immune cells and keratinocytes. Recently, it has been reported that IL-23 induces CCR6+ γδ T cells, which have the pivotal role in psoriasis-like skin inflammation in mice of producing IL-17A and IL-22. Langerhans cells (LCs) are a subset of dendritic cells that reside in the epidermis and regulate immune responses. The role of LCs has been extensively investigated in contact hypersensitivity, but their role in psoriasis remains to be clarified. In this study, we focused on Th17-related factors and assessed the role of LCs and γδ T cells in the development of psoriasis using a mouse psoriasis model triggered by topical application of imiquimod (IMQ). LC depletion by means of diphtheria toxin (DT) in Langerin DT receptor-knocked-in mice suppressed hyperkeratosis, parakeratosis, and ear swelling in the IMQ-treated regions. In addition, LC-depleted mice showed decreased levels of Th17-related cytokines in IMQ-treated skin lesions. Moreover, the IMQ-treated skin of LC-depleted mice showed a decreased number of IL-17A-producing CCR6+ γδ T cells. These results suggest that LCs are required for the development of psoriasis-like lesions induced by IMQ in mice.

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Aminoquinolines / pharmacology
  • Animals
  • Dermatitis, Contact / immunology
  • Disease Models, Animal
  • Imiquimod
  • Interleukin-12 / immunology
  • Interleukin-12 / metabolism
  • Interleukin-17 / genetics
  • Interleukin-17 / immunology*
  • Interleukin-17 / metabolism
  • Interleukin-23 Subunit p19 / genetics
  • Interleukin-23 Subunit p19 / immunology*
  • Interleukin-23 Subunit p19 / metabolism
  • Interleukins / genetics
  • Interleukins / immunology
  • Interleukins / metabolism
  • Langerhans Cells / cytology
  • Langerhans Cells / immunology*
  • Langerhans Cells / metabolism
  • Lymph Nodes / cytology
  • Lymph Nodes / immunology
  • Mice
  • Mice, Inbred C57BL
  • Organ Culture Techniques
  • Psoriasis / chemically induced
  • Psoriasis / immunology*
  • RNA, Messenger / metabolism
  • Receptors, Antigen, T-Cell, gamma-delta / immunology*
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism
  • Receptors, CCR6 / immunology
  • Receptors, CCR6 / metabolism
  • Skin / cytology
  • Skin / immunology
  • Transplantation Chimera / immunology

Substances

  • Adjuvants, Immunologic
  • Aminoquinolines
  • CCR6 protein, mouse
  • Il17a protein, mouse
  • Il23a protein, mouse
  • Interleukin-17
  • Interleukin-23 Subunit p19
  • Interleukins
  • RNA, Messenger
  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, CCR6
  • Interleukin-12
  • Imiquimod
  • interleukin-22