2. Academic Validation
  3. NFATc1 supports imiquimod-induced skin inflammation by suppressing IL-10 synthesis in B cells

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

  • Nat Commun. 2016 May 25;7:11724. doi: 10.1038/ncomms11724.
Hani Alrefai 1 2 3,  Khalid Muhammad 1,  Ronald Rudolf 1,  Duong Anh Thuy Pham 1,  Stefan Klein-Hessling 1,  Amiya K Patra 1,  Andris Avots 1,  Valesca Bukur 4,  Ugur Sahin 4 5,  Stefan Tenzer 6,  Matthias Goebeler 2,  Andreas Kerstan 2,  Edgar Serfling 1
Affiliations

Affiliations

  • 1 Department of Molecular Pathology, Institute of Pathology, Julius-Maximilians-University, Würzburg D-97080, Germany.
  • 2 Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, Würzburg D-97080, Germany.
  • 3 Faculty of Medicine, Department of Medical Biochemistry, Liver Laboratory, Mansoura University, Mansoura 35516, Egypt.
  • 4 TRON gGmbH-Translational Oncology, Johannes-Gutenberg-University Medical Center, Mainz D-55131, Germany.
  • 5 Johannes-Gutenberg-University Medical Center gGmbH, Mainz D-55131, Germany.
  • 6 Institute for Immunology, University Medical Center, Johannes-Gutenberg-University, Mainz D-55131, Germany.
PMID: 27222343 DOI: 10.1038/ncomms11724
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.

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