Over the past 50 years, the frequency of allergies and
autoimmune diseases has risen rapidly, but it’s not clear why. In a study published
in Science Translational Medicine, researchers
point to a possible culprit: salt. The authors found in lab experiments that
high concentrations of sodium chloride can influence the differentiation of T
helper 2 (Th2) cells, the immune cells responsible for allergies, and that high
levels of salt are present in the affected skin of people with atopic
dermatitis, an allergic skin condition.
Hay fever and atopic dermatitis have both increased more
than two-fold since the 1970s, an upsurge that researchers do not attribute to
greater awareness or diagnosis. This recent increase in the incidence of
allergic diseases is much too fast to be explained by genetic changes, so it’s
more likely to be due to an environmental or behavioral cause, coauthor Christina
Zielinski of the Technical University of Munich told The
Scientist. “One thing that also changed within the last fifty [to] sixty
years is our diet. We are eating much more fast food, and this also includes
much more salt, so that’s how we became interested in the question of whether
salt can modulate the immune system,” she says.
Zielinski and her colleagues started by upping the levels of
sodium chloride in the tissue culture medium used to grow either human
CD4-positive memory T cells, which give off a complex set of chemical signals
based on previous exposure to antigens, or naïve T cells, which have not been
exposed to antigens before. In both cell types, the salt boosted the abundance
of cytokines and transcription factors specific to Th2 cells, indicating that
high salinity promotes Th2 cell differentiation. The researchers also found
that the effects of the salt seemed to enhance Th2-related programmes via two
salt-sensitive transcription factors.
The authors next compared salt levels in the skin of adults
with atopic dermatitis. Lesioned skin had sodium concentrations 30-fold higher
than the patients’ unlesioned skin and skin from healthy controls. The team
also investigated sodium levels in affected and unaffected skin of people with
psoriasis. While both atopic dermatitis and psoriasis are both chronic
inflammatory skin conditions, psoriasis is mediated by a different type of T
helper cells. They found no difference in salt concentration in psoriatic
lesions and unaffected skin, which led them to rule out a role for inflammation
in the differences in sodium that they observed in people with atopic
“We were very surprised because atopic dermatitis is . . .
very intensely investigated, and no one has ever considered sodium chloride to
play a role,” says Zielinski. She adds that the next steps will be to
investigate the connection between salt and allergies.
According to Chuan Wu, an immunologist at the National
Cancer Institute who did not participate in the work, this connection could
involve nearby epidermal and dermal cells, as well as the skin microbiome. “The
skin is a big mucosal surface, colonised with a huge amount of microbes, [so
investigating] whether . . . the Th2 response is somehow connected to the skin
bacteria could be interesting,” he says.
The authors discuss in the study that people with atopic
dermatitis often have an overgrowth of Staphylococcus aureus on their
skin, which has gone unexplained until now.
Mackay points out that the gut microbiome could also be
involved, as high salt diets have previously been shown to have effects on
intestinal microbes. “Is it salt from the diet somehow affecting atopic
dermatitis? Or is there a gut connection here that they haven’t explored yet?”
“This connection to the diet is still very speculative.
There are some correlations and associations, but the definite proof is still
missing,” says Zielinski. “It could be that the sodium accumulation in the skin
follows some autonomous skin-intrinsic rules, which are completely independent
Matthias et al., “Sodium is an ionic checkpoint for human TH2 cells and shapes
the atopic skin microenvironment,” Science Translational Medicine. Published
20 February 2019.