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Monocyte-derived inflammatory Langerhans cells and dermal dendritic cells mediate psoriasis-like inflammation

Author

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  • Tej Pratap Singh

    (Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, US National Institutes of Health)

  • Howard H. Zhang

    (Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, US National Institutes of Health)

  • Izabela Borek

    (Institute of Pathophysiology and Immunology, Medical University of Graz)

  • Peter Wolf

    (Medical University of Graz)

  • Michael N. Hedrick

    (Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, US National Institutes of Health)

  • Satya P. Singh

    (Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, US National Institutes of Health)

  • Brian L. Kelsall

    (Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, US National Institutes of Health)

  • Bjorn E. Clausen

    (Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg-University Mainz)

  • Joshua M. Farber

    (Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, US National Institutes of Health)

Abstract

Dendritic cells (DCs) have been implicated in the pathogenesis of psoriasis but the roles for specific DC subsets are not well defined. Here we show that DCs are required for psoriasis-like changes in mouse skin induced by the local injection of IL-23. However, Flt3L-dependent DCs and resident Langerhans cells are dispensable for the inflammation. In epidermis and dermis, the critical DCs are TNF-producing and IL-1β-producing monocyte-derived DCs, including a population of inflammatory Langerhans cells. Depleting Ly6Chi blood monocytes reduces DC accumulation and the skin changes induced either by injecting IL-23 or by application of the TLR7 agonist imiquimod. Moreover, we find that IL-23-induced inflammation requires expression of CCR6 by DCs or their precursors, and that CCR6 mediates monocyte trafficking into inflamed skin. Collectively, our results imply that monocyte-derived cells are critical contributors to psoriasis through production of inflammatory cytokines that augment the activation of skin T cells.

Suggested Citation

  • Tej Pratap Singh & Howard H. Zhang & Izabela Borek & Peter Wolf & Michael N. Hedrick & Satya P. Singh & Brian L. Kelsall & Bjorn E. Clausen & Joshua M. Farber, 2016. "Monocyte-derived inflammatory Langerhans cells and dermal dendritic cells mediate psoriasis-like inflammation," Nature Communications, Nature, vol. 7(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13581
    DOI: 10.1038/ncomms13581
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