PuSH - Publication Server of Helmholtz Zentrum München: Sodium chloride is an ionic checkpoint for human T<sub>H</sub>2 cells and shapes the atopic skin microenvironment.

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Matthias, J.* ; Maul, J.* ; Noster, R.* ; Meinl, H.* ; Chao, Y.Y.* ; Gerstenberg, H.* ; Jeschke, F.* ; Gasparoni, G.* ; Welle, A.* ; Walter, J.* ; Nordström, K.* ; Eberhardt, K.* ; Renisch, D.* ; Donakonda, S.* ; Knolle, P.* ; Soll, D.* ; Grabbe, S.* ; Garzorz-Stark, N. ; Eyerich, K. ; Biedermann, T. ; Baumjohann, D.* ; Zielinski, C.E.*

Sodium chloride is an ionic checkpoint for human T_H2 cells and shapes the atopic skin microenvironment.

Sci. Transl. Med. 11:eaau0683 (2019)

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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 (T(H)17) cells with implications for autoimmune diseases such as multiple sclerosis. Here, we demonstrate that sodium chloride also potently promotes T(H)2 cell responses on multiple regulatory levels. Sodium chloride enhanced interleukin-4 (IL-4) and IL-13 production while suppressing interferon-gamma (IFN-gamma) production in memory T cells. It diverted alternative T cell fates into the T(H)2 cell phenotype and also induced de novo T(H)2 cell polarization from naive T cell precursors. Mechanistically, sodium chloride exerted its effects via the osmosensitive transcription factor NFAT5 and the kinase SGK-1, which regulated T(H)2 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 T(H)2 cell responses, the orchestrators of atopic diseases.

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