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NFATc1 supports imiquimod-induced skin inflammation by suppressing IL-10 synthesis in B cells

Author

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  • Hani Alrefai

    (Institute of Pathology, Julius-Maximilians-University
    Venereology and Allergology, University Hospital Würzburg
    Faculty of Medicine, Liver Laboratory, Mansoura University)

  • Khalid Muhammad

    (Institute of Pathology, Julius-Maximilians-University)

  • Ronald Rudolf

    (Institute of Pathology, Julius-Maximilians-University)

  • Duong Anh Thuy Pham

    (Institute of Pathology, Julius-Maximilians-University)

  • Stefan Klein-Hessling

    (Institute of Pathology, Julius-Maximilians-University)

  • Amiya K. Patra

    (Institute of Pathology, Julius-Maximilians-University)

  • Andris Avots

    (Institute of Pathology, Julius-Maximilians-University)

  • Valesca Bukur

    (TRON gGmbH-Translational Oncology, Johannes-Gutenberg-University Medical Center)

  • Ugur Sahin

    (TRON gGmbH-Translational Oncology, Johannes-Gutenberg-University Medical Center
    Johannes-Gutenberg-University Medical Center gGmbH)

  • Stefan Tenzer

    (Institute for Immunology, University Medical Center, Johannes-Gutenberg-University)

  • Matthias Goebeler

    (Venereology and Allergology, University Hospital Würzburg)

  • Andreas Kerstan

    (Venereology and Allergology, University Hospital Würzburg)

  • Edgar Serfling

    (Institute of Pathology, Julius-Maximilians-University)

Abstract

Epicutaneous application of Aldara cream containing the TLR7 agonist imiquimod (IMQ) to mice induces skin inflammation that exhibits many aspects of psoriasis, an inflammatory human skin disease. Here we show that mice depleted of B cells or bearing interleukin (IL)-10-deficient B cells show a fulminant inflammation upon IMQ exposure, whereas ablation of NFATc1 in B cells results in a suppression of Aldara-induced inflammation. In vitro, IMQ induces the proliferation and IL-10 expression by B cells that is blocked by BCR signals inducing NFATc1. By binding to HDAC1, a transcriptional repressor, and to an intronic site of the Il10 gene, NFATc1 suppresses IL-10 expression that dampens the production of tumour necrosis factor-α and IL-17 by T cells. These data indicate a close link between NFATc1 and IL-10 expression in B cells and suggest NFATc1 and, in particular, its inducible short isoform, NFATc1/αA, as a potential target to treat human psoriasis.

Suggested Citation

  • Hani Alrefai & Khalid Muhammad & Ronald Rudolf & Duong Anh Thuy Pham & Stefan Klein-Hessling & Amiya K. Patra & Andris Avots & Valesca Bukur & Ugur Sahin & Stefan Tenzer & Matthias Goebeler & Andreas , 2016. "NFATc1 supports imiquimod-induced skin inflammation by suppressing IL-10 synthesis in B cells," Nature Communications, Nature, vol. 7(1), pages 1-13, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11724
    DOI: 10.1038/ncomms11724
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