Specific roles for dendritic cell subsets during initiation and progression of psoriasis

Elisabeth Glitzner; Ana Korosec; Patrick M Brunner; Barbara Drobits; Nicole Amberg; Helia B Schonthaler; Tamara Kopp; Erwin F Wagner; Georg Stingl; Martin Holcmann; Maria Sibilia

doi:10.15252/emmm.201404114

Specific roles for dendritic cell subsets during initiation and progression of psoriasis

EMBO Mol Med. 2014 Oct;6(10):1312-27. doi: 10.15252/emmm.201404114.

Affiliations

¹ Department of Medicine I, Comprehensive Cancer Center Institute of Cancer Research Medical University of Vienna, Vienna, Austria.
² Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases, Medical University of Vienna, Vienna, Austria.
³ BBVA Foundation-CNIO Cancer Cell Biology Programme Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
⁴ Department of Medicine I, Comprehensive Cancer Center Institute of Cancer Research Medical University of Vienna, Vienna, Austria maria.sibilia@meduniwien.ac.at.

Abstract

Several subtypes of APCs are found in psoriasis patients, but their involvement in disease pathogenesis is poorly understood. Here, we investigated the contribution of Langerhans cells (LCs) and plasmacytoid DCs (pDCs) in psoriasis. In human psoriatic lesions and in a psoriasis mouse model (DKO* mice), LCs are severely reduced, whereas pDCs are increased. Depletion of pDCs in DKO* mice prior to psoriasis induction resulted in a milder phenotype, whereas depletion during active disease had no effect. In contrast, while depletion of Langerin-expressing APCs before disease onset had no effect, depletion from diseased mice aggravated psoriasis symptoms. Disease aggravation was due to the absence of LCs, but not other Langerin-expressing APCs. LCs derived from DKO* mice produced increased IL-10 levels, suggesting an immunosuppressive function. Moreover, IL-23 production was high in psoriatic mice and further increased in the absence of LCs. Conversely, pDC depletion resulted in reduced IL-23 production, and therapeutic inhibition of IL-23R signaling ameliorated disease symptoms. Therefore, LCs have an anti-inflammatory role during active psoriatic disease, while pDCs exert an instigatory function during disease initiation.

Keywords: AP‐1; IL‐23; Langerhans cells; plasmacytoid dendritic cells; psoriasis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adjuvants, Immunologic / pharmacology
Aminoquinolines / pharmacology
Animals
Antibodies, Monoclonal / immunology
Antibodies, Monoclonal / pharmacology
Antigen-Presenting Cells / immunology*
Antigen-Presenting Cells / metabolism
Bone Marrow Transplantation
Dendritic Cells / immunology*
Dendritic Cells / metabolism
Disease Progression
Flow Cytometry
Humans
Imiquimod
Interleukin-10 / immunology
Interleukin-10 / metabolism
Interleukin-23 / immunology
Interleukin-23 / metabolism
Langerhans Cells / immunology*
Langerhans Cells / metabolism
Mice, Inbred C57BL
Mice, Knockout
Microscopy, Confocal
Proto-Oncogene Proteins c-jun / deficiency
Proto-Oncogene Proteins c-jun / genetics
Proto-Oncogene Proteins c-jun / immunology
Psoriasis / genetics
Psoriasis / immunology*
Psoriasis / prevention & control
Receptors, Interleukin / immunology
Receptors, Interleukin / metabolism
Signal Transduction / drug effects
Signal Transduction / immunology
Skin / drug effects
Skin / immunology
Skin / pathology
Transcription Factors / deficiency
Transcription Factors / genetics
Transcription Factors / immunology

Substances

Adjuvants, Immunologic
Aminoquinolines
Antibodies, Monoclonal
Interleukin-23
JunB protein, mouse
Proto-Oncogene Proteins c-jun
Receptors, Interleukin
Transcription Factors
interleukin-23 receptor, mouse
Interleukin-10
Imiquimod