The DOI matches its Crossref record; 63 of the 63 references it cites were found in a registry or an index.
Sodium chloride inhibits the suppressive function of FOXP3+ regulatory T cells
Open accessAbstract
FOXP3+ Tregs are central for the maintenance of self-tolerance and can be defective in autoimmunity. In multiple sclerosis and type-1 diabetes, dysfunctional self-tolerance is partially mediated by a population of IFNγ-secreting Tregs. It was previously reported that increased NaCl concentrations promote the induction of proinflammatory Th17 cells and that high-salt diets exacerbate experimental models of autoimmunity. Here, we have shown that increasing NaCl, either in vitro or in murine models via diet, markedly impairs Treg function. NaCl increased IFNγ secretion in Tregs, and reducing IFNγ - either by neutralization with anti-IFNγ antibodies or shRNA-mediated knockdown - restored suppressive activity in Tregs. The heightened IFNγ secretion and loss of Treg function were mediated by the serum/glucocorticoid-regulated kinase (SGK1). A high-salt diet also impaired human Treg function and was associated with the induction of IFNγ-secreting Tregs in a xenogeneic graft-versus-host disease model and in adoptive transfer models of experimental colitis. Our results demonstrate a putative role for an environmental factor that promotes autoimmunity by inducing proinflammatory responses in CD4 effector cells and Treg pathways.
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Cites
The Role of Tumoral FOXP3 on Cell Proliferation, Migration, and Invasion in Gastric Cancer
Zhang, L., Xu, J., Zhang, X., Zhang, Y., Wang, L., Huang, X., & Xu, Z. (2017) · Cellular Physiology and Biochemistry · doi:10.1159/000479442 · Cited by 4,088
The Effect of Diet on the Human Gut Microbiome: A Metagenomic Analysis in Humanized Gnotobiotic Mice
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FOXP3+ regulatory T cells in the human immune system
Sakaguchi, S., Miyara, M., Costantino, C. M., & Hafler, D. A. (2010) · Nature Reviews Immunology · doi:10.1038/nri2785 · Cited by 2,439
Self-citationDiet Drives Convergence in Gut Microbiome Functions Across Mammalian Phylogeny and Within Humans
Muegge, B. D., Kuczynski, J., Knights, D., Clemente, J. C., González, A., Fontana, L., Henrissat, B., Knight, R., & Gordon, J. I. (2011) · Science · doi:10.1126/science.1198719 · Cited by 1,988
Loss of Functional Suppression by CD4+CD25+ Regulatory T Cells in Patients with Multiple Sclerosis
Viglietta, V., Baecher-Allan, C., Weiner, H. L., & Hafler, D. A. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20031579 · Cited by 1,856
Self-citationAsseman, C., Mauze, S., Leach, M. W., Coffman, R. L., & Powrie, F. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.190.7.995 · Cited by 1,615
Foxp3+CD25+CD4+ natural regulatory T cells in dominant self‐tolerance and autoimmune disease
Sakaguchi, S., Ono, M., Setoguchi, R., Yagi, H., Hori, S., Fehervari, Z., Shimizu, J., Takahashi, T., & Nomura, T. (2006) · Immunological Reviews · doi:10.1111/j.0105-2896.2006.00427.x · Cited by 1,555
Sodium chloride drives autoimmune disease by the induction of pathogenic TH17 cells
Kleinewietfeld, M., Manzel, A., Titze, J., Kvakan, H., Yosef, N., Linker, R. A., Muller, D. N., & Hafler, D. A. (2013) · Nature · doi:10.1038/nature11868 · Cited by 1,394
Self-citationAssociation scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants
Wellcome Trust Case Control Consortium, & The Australo-Anglo-American Spondylitis Consortium (TASC) (2007) · Nature Genetics · doi:10.1038/ng.2007.17 · Cited by 1,374
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Cited by
Salt-responsive gut commensal modulates TH17 axis and disease
Wilck, N., Matus, M. G., Kearney, S. M., Olesen, S. W., Forslund, K., Bartolomaeus, H., Haase, S., Mähler, A., Balogh, A., Markó, L., et al. (2017) · Nature · doi:10.1038/nature24628 · Cited by 1,310
Self-citationRegulatory T cells in autoimmune disease
Dominguez-Villar, M., & Hafler, D. A. (2018) · Nature Immunology · doi:10.1038/s41590-018-0120-4 · Cited by 713
Self-citationSalt Reduction to Prevent Hypertension and Cardiovascular Disease
He, F. J., Tan, M., Ma, Y., & MacGregor, G. A. (2020) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2019.11.055 · Cited by 589
The Role of Astrocytes in Multiple Sclerosis
Ponath, G., Park, C., & Pitt, D. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00217 · Cited by 359
Dietary salt promotes neurovascular and cognitive dysfunction through a gut-initiated TH17 response
Faraco, G., Brea, D., Garcia-Bonilla, L., Wang, G., Racchumi, G., Chang, H., Buendia, I., Santisteban, M. M., Segarra, S. G., Koizumi, K., et al. (2018) · Nature Neuroscience · doi:10.1038/s41593-017-0059-z · Cited by 343
Metadata
- Authors
- Hernandez, A. L., Kitz, A., Wu, C., Lowther, D. E., Rodriguez, D. M., Vudattu, N., Deng, S., Herold, K. C., Kuchroo, V. K., Kleinewietfeld, M., & Hafler, D. A.
- Venue
- Journal of Clinical Investigation
- Published
- 2015-10-20
- Volume
- 125
- Issue
- 11
- Pages
- 4212-4222
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- OpenAlex
- W1824732500
- Cited by
- 338
- References
- 63
- FWCI
- 15.25
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Hernandez, A. L., Kitz, A., Wu, C., Lowther, D. E., Rodriguez, D. M., Vudattu, N., Deng, S., Herold, K. C., Kuchroo, V. K., Kleinewietfeld, M., & Hafler, D. A. (2015). Sodium chloride inhibits the suppressive function of FOXP3+ regulatory T cells. Journal of Clinical Investigation. https://doi.org/10.1172/jci81151
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