Research ArticleALLERGY

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

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Science Translational Medicine  20 Feb 2019:
Vol. 11, Issue 480, eaau0683
DOI: 10.1126/scitranslmed.aau0683

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Salting T cells’ game

Sodium chloride can encourage TH17 differentiation in CD4 T cells. Matthias et al. now show that sodium chloride can also promote TH2 responses, which are central in allergic diseases. They measured effects of different concentrations of sodium chloride on memory and naïve human T cells as well as mouse cells. Collectively, higher sodium chloride enforced a TH2 transcriptional and phenotypic program. Interestingly, lesional skin from atopic dermatitis patients, but not psoriasis patients, had elevated sodium. These findings suggest that sodium chloride could be a potential player in the progression of allergy in the skin.

Abstract

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.

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