Sodium chloride is an ionic checkpoint for human TH2 cells and shapes the atopic skin microenvironment

The incidence of allergic diseases has increased over the past 50 years, likely due to environmental factors. However, the nature of these factors and the mode of action by which they induce the type 2 immune deviation characteristic of atopic diseases remain unclear. It has previously been reported...

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Bibliographic Details
Published in:Science translational medicine 2019-02, Vol.11 (480)
Main Authors: Matthias, Julia, Maul, Julia, Noster, Rebecca, Meinl, Hanna, Chao, Ying-Yin, Gerstenberg, Heiko, Jeschke, Florian, Gasparoni, Gilles, Welle, Anna, Walter, Jörn, Nordström, Karl, Eberhardt, Klaus, Renisch, Dennis, Donakonda, Sainitin, Knolle, Percy, Soll, Dominik, Grabbe, Stephan, Garzorz-Stark, Natalie, Eyerich, Kilian, Biedermann, Tilo, Baumjohann, Dirk, Zielinski, Christina E
Format: Article
Language:eng ; jpn
Subjects:
Allergic diseases
Atopic dermatitis
Autoimmune diseases
Environmental factors
Helper cells
Immune deviation
Immunological memory
Interleukin 13
Interleukin 4
Lymphocytes T
Memory cells
Multiple sclerosis
Osmotic pressure
Phenotypes
Polarization
Sodium chloride
Transcription factors
γ-Interferon
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Summary:The incidence of allergic diseases has increased over the past 50 years, likely due to environmental factors. However, the nature of these factors and the mode of action by which they induce the type 2 immune deviation characteristic of atopic diseases remain unclear. It has previously been reported that dietary sodium chloride promotes the polarization of T helper 17 (TH17) cells with implications for autoimmune diseases such as multiple sclerosis. Here, we demonstrate that sodium chloride also potently promotes TH2 cell responses on multiple regulatory levels. Sodium chloride enhanced interleukin-4 (IL-4) and IL-13 production while suppressing interferon-γ (IFN-γ) production in memory T cells. It diverted alternative T cell fates into the TH2 cell phenotype and also induced de novo TH2 cell polarization from naïve T cell precursors. Mechanistically, sodium chloride exerted its effects via the osmosensitive transcription factor NFAT5 and the kinase SGK-1, which regulated TH2 signature cytokines and master transcription factors in hyperosmolar salt conditions. The skin of patients suffering from atopic dermatitis contained elevated sodium compared to nonlesional atopic and healthy skin. These results suggest that sodium chloride represents a so far overlooked cutaneous microenvironmental checkpoint in atopic dermatitis that can induce TH2 cell responses, the orchestrators of atopic diseases.
ISSN:1946-6234
1946-3242
1946-6242
DOI:10.1126/scitranslmed.aau0683