Researchers gained new insight into how an immune
cell involved in several autoimmune disorders is
regulated. Among their findings was a potential link
with salt consumption.
Autoimmune diseases arise when the immune system,
which normally protects the body from invading
microbes, mistakenly attacks the body’s own tissues.
These diseases include type 1 diabetes, inflammatory
bowel diseases and multiple sclerosis. Researchers
have found many genetic variants that affect the
risk of developing autoimmune diseases. However, a
number of environmental factors, including viral
infections, smoking and low vitamin D levels, are
known to trigger such diseases in susceptible
people.
Immune cells called T helper 17 (Th17) cells help us
fight infection, but they’ve also been linked with
several autoimmune disorders. Th17 cells, along with
other types of helper T cells, arise from naive T
cells. Researchers had identified specific factors
that induce the development of Th17 cells, but the
downstream factors that guide and control the cells’
development were largely unknown.
Several research groups—at Yale University, the
Broad Institute, Harvard University, MIT, Brigham
and Women's Hospital, and others—have been exploring
the development of Th17 cells. Their work has been
funded by several NIH components, including the
National Institute of Allergy and Infectious
Diseases (NIAID), National Institute of Neurological
Disorders and Stroke (NINDS) and National Human
Genome Research Institute (NHGRI). A trio of new
papers describing their findings was published
online in Nature on March 6, 2013.
A team led by Dr. Aviv Regev studied genes expressed
at different time points during Th17 cell
development. Computer modeling helped to identify 3
major waves of gene expression over time. They
detected almost 1,300 genes involved in over 10,000
interactions, with 71 regulators. Using silicon
nanowires to deliver short interfering RNA (siRNA)
into naive T cells, the researchers were able to
interfere with the expression of specific genes to
further validate the internal network used to build
Th17 cells. They validated 39 of the regulatory
factors with this new technique.
Using information from the network analysis, a
related team led by Dr. Vijay K. Kuchroo studied
gene expression in developing Th17 cells after
activation of a receptor that involves the cells in
autoimmunity. They identified a key protein in the
cell’s development called serum glucocorticoid
kinase 1 (SGK1). To test its role in autoimmune
disease, they examined a mouse disease that
resembles human multiple sclerosis. Mice lacking
SGK1 had less severe symptoms and significantly
reduced rates of the disease, known as experimental
autoimmune encephalomyelitis (EAE).
SGK1 is known to regulate sodium intake in other
cells, raising the possibility that sodium may
affect Th17 cell development. In a high-salt
solution, naive T cells expressed the gene for SGK1
at increased levels, along with other genes
associated with Th17 development. Mice fed a
high-salt diet showed a marked increase in Th17
cells after 3 weeks. Mice on a high-salt diet also
had more severe EAE than those fed a normal diet.
Mice lacking SGK1, in contrast, didn’t show similar
increases when fed a high-salt diet.
In the third study, a group led by Dr. David Hafler
discovered that increased salt concentrations
boosted the development of both mouse and human
naive T cells into Th17 cells. This led them to
explore the molecular pathways involved in Th17 cell
development. They also found that mice fed a
high-salt diet developed a more severe form of EAE.
The incidence of certain autoimmune diseases in our
society, including multiple sclerosis and type 1
diabetes, has been rising over recent decades. This
research suggests that one factor may be that we now
eat more processed foods with high levels of salt.
“It's premature to say, ‘You shouldn't eat salt
because you'll get an autoimmune disease.’” Regev
says. “We're putting forth an interesting hypothesis—a
connection between salt and autoimmunity—that now
must be tested through careful epidemiological
studies in humans.”
“Once we have a more nuanced understanding of the
development of the pathogenic Th17 cells, we may be
able to pursue ways to regulate them or their
function,” Kuchroo adds.
Hafler’s group has begun preliminary studies to
determine whether restricting salt intake can
influence autoimmune disease in people. Hafler says,
“I have already begun to suggest to my patients with
multiple sclerosis that it may not be bad to
restrict their dietary salt intake.”
For more informations
http://www.nih.gov/
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