Features | Partner Sites | Information | LinkXpress
Sign In
BioConferenceLive
JIB
GLOBETECH PUBLISHING

Increased Dietary Salt Causes Autoimmune Diseases by Stimulating Formation of Proinflammatory TH17 Cells

By BiotechDaily International staff writers
Posted on 19 Mar 2013
Three recent papers linked elevated dietary salt to the development of autoimmune diseases such as multiple sclerosis and type I diabetes by demonstrating the relationship between salt levels and the generation of T helper 17 (TH17) cells.

TH17 cells (interleukin-17 (IL-17)-producing helper T cells) are highly pro-inflammatory cells that are critical for clearing extracellular pathogens and for inducing multiple autoimmune diseases. To study the effect of salt concentration on TH17 cell metabolism investigators at Harvard Medical School (Boston, MA, USA) and Yale School of Medicine (New Haven, CT, USA) worked with cell cultures and with mouse populations where it was easy to adjust the level of dietary salt.

Details of the research and results were published in three papers that appeared in the March 6, 2013, online edition of the journal Nature. Among other factors, the investigators identified the protein serum glucocorticoid kinase 1 (SGK1), which is known to regulate salt levels in other types of cells, as a TH17-signal. The researchers found that mouse cells cultured in high-salt conditions had higher SGK1 expression and produced more TH17 cells than those grown in normal conditions. A modest increase in salt concentration induced SGK1 expression, promoted interleukin-23R expression, and enhanced TH17 cell differentiation in vitro and in vivo, accelerating the development of autoimmunity.

High-salt conditions activated the p38/MAPK pathway involving nuclear factor of activated T cells 5 (NFAT5; also called TONEBP) and SGK1 during cytokine-induced TH17 polarization. Gene silencing or chemical inhibition of p38/MAPK, NFAT5, or SGK1 abolished the high-salt-induced TH17 cell development. TH17 cells generated under high-salt conditions displayed a highly pathogenic and stable phenotype characterized by the upregulation of the proinflammatory cytokines.

"Humans were genetically selected for conditions in sub-Saharan Africa, where there was no salt," said senior author Dr. David Hafler, professor of neurology and immunobiology at Yale School of Medicine. "Today, Western diets all have high salt content and that has led to increase in hypertension and perhaps autoimmune disease as well. These are not diseases of bad genes alone or diseases caused by the environment, but diseases of a bad interaction between genes and the environment."

"Test-tube cell biology is performed based on the salt levels found in blood and not in the tissues where immune cells ultimately travel to fight infections," said Dr. Hafler. "That may have been a reason salt's role in autoimmunity has gone undetected. We may have been using the wrong concentrations of salt in our experiments for the past half-century. Nature did not want immune cells to become turned on in the pipeline, so perhaps blood salt levels are inhibitory."

Related Links:

Harvard Medical School
Yale School of Medicine



comments powered by Disqus

Channels

Drug Discovery

view channel
Image: The European Commission has approved the use of Avastin combined with chemotherapy as a treatment for women with recurrent ovarian cancer (Photo courtesy of Genentech).

Drug for Treatment of Platinum Resistant Recurrent Ovarian Cancer Approved for Use in Europe

For the first time in more than 15 years the European Commission (EC) has approved a new therapeutic option for the most difficult to treat form of ovarian cancer. Ovarian cancer causes more deaths... Read more

Therapeutics

view channel
Image: This type of electronic pacemaker could become obsolete if induction of biological pacemaker cells by gene therapy proves successful (Photo courtesy of Wikimedia Commons).

Gene Therapy Induces Functional Pacemaker Cells in Pig Heart Failure Model

Cardiovascular disease researchers working with a porcine heart failure model have demonstrated the practicality of using gene therapy to replace implanted electronic pacemakers to regulate heartbeat.... Read more

Lab Technologies

view channel
Image: Neurons (greenish yellow) attach to silk-based scaffold (blue) creating functional networks throughout the scaffold pores (dark areas) (Photo courtesy of Tufts University).

Functional 3D Brain-Like Tissue Model Bioengineered

Researchers recently reported on the development of the first complex, three-dimensional (3D) model comprised of brain-like cortical tissue that displays biochemical and electrophysiologic responses, and... Read more

Business

view channel

Global Computational Biology Sector Expected to Reach over USD 4 Billion by 2020

The global market for computational biology is expected to reach USD 4.285 billion by 2020 growing at a compound annual growth rate (CAGR) of 21.1%, according to new market research. Steady surge in the usage and application of computational biology for bioinformatics R&D programs designed for sequencing genomes... Read more
 
Copyright © 2000-2014 Globetech Media. All rights reserved.