Sodium chloride is an ionic checkpoint for human TH 2 cells and shapes the atopic skin microenvironment

Science Translational Medicine
J. MatthiasChristina E Zielinski

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 chlorid...Continue Reading

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Citations

Jul 6, 2019·European Journal of Immunology·Julia Matthias, Christina E Zielinski
Jun 23, 2020·PLoS Biology·Patrick NeubertJonathan Jantsch
Aug 1, 2019·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Rik H G Olde EngberinkLiffert Vogt
Dec 6, 2019·JCI Insight·Agnes SchröderJonathan Jantsch
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Jun 27, 2019·Nature Reviews. Nephrology·Nicola WilckDominik N Müller
Mar 28, 2020·Science Translational Medicine·Katarzyna JobinChristian Kurts
Jun 3, 2020·The Journal of Clinical Investigation·Julia MatthiasChristina E Zielinski
Dec 18, 2020·Frontiers in Immunology·Ali AminiPaul Klenerman
Oct 17, 2020·Immunology·Silvia CerboniSuman Mitra
May 14, 2021·Science Advances·Yuanhui HuangVasilis Ntziachristos
May 9, 2021·Trends in Immunology·Katarzyna JobinChristian Kurts
Jul 9, 2021·The Journal of Investigative Dermatology·András MaifeldLajos Markó
Sep 28, 2021·Frontiers in Immunology·Luka KrampertJonathan Jantsch
Dec 1, 2021·The Journal of Clinical Hypertension·Zhiyi MaYuanyuan Chen

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