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

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 fulmi...

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Bibliographic Details
Published in:Nature communications 2016-05, Vol.7 (1), p.11724-11724, Article 11724
Main Authors: Alrefai, Hani, Muhammad, Khalid, Rudolf, Ronald, Pham, Duong Anh Thuy, Klein-Hessling, Stefan, Patra, Amiya K., Avots, Andris, Bukur, Valesca, Sahin, Ugur, Tenzer, Stefan, Goebeler, Matthias, Kerstan, Andreas, Serfling, Edgar
Format: Article
Language:English
Subjects:
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14/1
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631/250/1619/40
631/250/249/1313/1758
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64/60
82/51
Cytokines
Humanities and Social Sciences
Lymphocytes
multidisciplinary
Proteins
Psoriasis
Science
Science (multidisciplinary)
Skin diseases
Tumor necrosis factor-TNF
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Summary: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. Regulatory B cells are important for preventing skin autoimmunity. Here the authors show that NFATc1 suppresses IL-10 transcription in regulatory B cells, and inhibiting NFATc1 decreases immunopathology in a mouse model of imiquimod-induced skin inflammation.
ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms11724