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Cited by 281

The DOI matches its Crossref record; 21 of the 21 references it cites were found in a registry or an index.

High salt reduces the activation of IL-4– and IL-13–stimulated macrophages

Open access
Binger, Katrina J., Gebhardt, Matthias, Heinig, Matthias, Rintisch, Carola, Schroeder, Agnes, Neuhofer, Wolfgang, Hilgers, Karl, Manzel, Arndt, Schwartz, Christian, Kleinewietfeld, Markus, Voelkl, Jakob, Schatz, Valentin, Linker, Ralf A., Lang, Florian, Voehringer, David, Wright, Mark D., Hubner, Norbert, Dechend, Ralf, Jantsch, Jonathan, Titze, Jens, Müller, Dominik N.·2015·Journal of Clinical Investigation

Abstract

A high intake of dietary salt (NaCl) has been implicated in the development of hypertension, chronic inflammation, and autoimmune diseases. We have recently shown that salt has a proinflammatory effect and boosts the activation of Th17 cells and the activation of classical, LPS-induced macrophages (M1). Here, we examined how the activation of alternative (M2) macrophages is affected by salt. In stark contrast to Th17 cells and M1 macrophages, high salt blunted the alternative activation of BM-derived mouse macrophages stimulated with IL-4 and IL-13, M(IL-4+IL-13) macrophages. Salt-induced reduction of M(IL-4+IL-13) activation was not associated with increased polarization toward a proinflammatory M1 phenotype. In vitro, high salt decreased the ability of M(IL-4+IL-13) macrophages to suppress effector T cell proliferation. Moreover, mice fed a high salt diet exhibited reduced M2 activation following chitin injection and delayed wound healing compared with control animals. We further identified a high salt-induced reduction in glycolysis and mitochondrial metabolic output, coupled with blunted AKT and mTOR signaling, which indicates a mechanism by which NaCl inhibits full M2 macrophage activation. Collectively, this study provides evidence that high salt reduces noninflammatory innate immune cell activation and may thus lead to an overall imbalance in immune homeostasis.

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Metadata

Authors
Binger, K. J., Gebhardt, M., Heinig, M., Rintisch, C., Schroeder, A., Neuhofer, W., Hilgers, K., Manzel, A., Schwartz, C., Kleinewietfeld, M., Voelkl, J., Schatz, V., Linker, R. A., Lang, F., Voehringer, D., Wright, M. D., Hubner, N., Dechend, R., Jantsch, J., Titze, J., & Müller, D. N.
Venue
Journal of Clinical Investigation
Published
2015-10-20
Volume
125
Issue
11
Pages
4223-4238
ISSN
  • 0021-9738 (ISSN-L)
  • 1558-8238
OpenAlex
W2139654366
Cited by
281
References
21
FWCI
11.82
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: High salt reduces the activation of IL-4– and IL-13–stimulated macrophages. https://app.cochat.ai/papers/10.1172/jci80919
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Binger, K. J., Gebhardt, M., Heinig, M., Rintisch, C., Schroeder, A., Neuhofer, W., Hilgers, K., Manzel, A., Schwartz, C., Kleinewietfeld, M., Voelkl, J., Schatz, V., Linker, R. A., Lang, F., Voehringer, D., Wright, M. D., Hubner, N., Dechend, R., Jantsch, J., . . . Müller, D. N. (2015). High salt reduces the activation of IL-4– and IL-13–stimulated macrophages. Journal of Clinical Investigation. https://doi.org/10.1172/jci80919

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.