18 August 2009
Oregon State University
A new study has concluded that one key
part of the immune system, the ability of
vitamin D to regulate
anti-bactericidal proteins, is so important that is has been
conserved through almost 60 million years of evolution and is shared
only by primates, including humans – but no other known animal
The fact that this vitamin-D mediated immune response has been
retained through millions of years of evolutionary selection, and is
still found in species ranging from squirrel monkeys to baboons and
humans, suggests that it must be critical to their survival,
Even though the "cathelicidin
antimicrobial peptide" has several different biological
activities in addition to killing pathogens, it's not clear which
one, or combination of them, makes vitamin D so essential to its
The research also provides further evidence of the biological
importance of adequate levels of vitamin D in humans and other
primates, even as some studies and experts suggest that more than 50
percent of the children and adults in the U.S. are deficient in
"the sunshine vitamin."
"The existence and importance of
this part of our immune response makes it clear that humans and
other primates need to maintain sufficient levels of vitamin D,"
said Adrian Gombart, an associate professor of
biochemistry and a principal investigator with the Linus
Pauling Institute at Oregon State University.
In a new study in the journal BMC
Genomics, researchers from
OSU and the Cedars-Sinai Medical
Center describe the presence of a genetic element that's specific to
primates and involved in the innate immune response.
They found it not only in humans and
their more recent primate ancestors, such as chimpanzees, but also
primates that split off on the evolutionary tree tens of millions of
years ago, such as old world and new world primates.
The genetic material – called an
Alu short interspersed element – is
part of what used to be thought of as "junk
DNA" and makes up more than 90 percent of the human
That genetic material, however, is now
understood to often play important roles in regulating and "turning
on" the expression of other genes.
In this case, the genetic element is believed to play a major role
in the proper function of the "innate" immune system in primates –
an ancient, first line of defense against bacteria, viruses and
other pathogens, in which the body recognizes something that
probably doesn't belong there, even though the specific pathogen may
never have been encountered before.
"Many people are familiar with the
role of our adaptive immune system, which is what happens when
we mount a defense against a new invader and then retain
antibodies and immunity in the future," Gombart said.
"That's what makes a
vaccine work. But also
very important is the innate immune system, the almost
immediate reaction your body has, for instance, when you get a
cut or a skin infection."
In primates, this action of "turning on"
an optimal response to microbial attack only works properly in the
presence of adequate vitamin D, which is actually a type of hormone
that circulates in the blood and signals to cells through a
Vitamin D is produced in large
amounts as a result of sun exposure, and is available in much
smaller amounts from
Vitamin D prevents the "adaptive" immune response from over-reacting
and reduces inflammation, and appears to suppress the immune
response. However, the function of the new genetic element
this research explored allows vitamin D to boost the innate
immune response by turning on an antimicrobial protein.
The overall effect may help to prevent
the immune system from overreacting.
"It's essential that we have both an
innate immune response that provides an immediate and front line
of defense, but we also have protection against an overreaction
by the immune system, which is what you see in sepsis and some
autoimmune or degenerative diseases," Gombart said.
"This is a very delicate balancing
act, and without sufficient levels of vitamin D you may not have
an optimal response with either aspect of the immune system."
After years of research, scientists are
continuing to find new roles that vitamin D plays in the human
body. It can regulate the actions of genes that are important to
bone health, calcium uptake, and inhibition of cell growth.
It helps regulate cell differentiation
and, of course, immune function.
"The antimicrobial peptide that
we're studying seems to be involved not just in killing
bacteria, but has other biological roles," Gombart said.
"It recruits other immune cells and
sort of sounds the alarm that something is wrong. It helps
promote development of blood vessels, cell growth and healing of
wounds. And it seems to have important roles in barrier tissues
such as skin and the digestive system. Vitamin D is very
important for the health of the skin and digestive system, and
cathelicidin antimicrobial peptide gene
under its regulation may be important in this function."
Any one, or some combination of those
biological roles may be why vitamin D-mediated regulation of the
antimicrobial peptide has been conserved in every primate species
ever examined for its presence, researchers said, and did not
disappear long ago through evolutionary variation and mutation.
The evolution of primates into many
different families and hundreds of species has been carefully
tracked through genetic, molecular sequence and fossil studies, but
the presence of this regulatory element in primates is still largely
the same as it's been for more than 50 million years.
The evolutionary survival of this genetic element and the placement
of the cathelicidin antimicrobial peptide gene under the
regulation of the vitamin D pathway,
"may enable suppression of
inflammation while potentiating innate immunity, thus maximizing
the overall immune response to a pathogen and minimizing damage
to the host," the researchers wrote in their conclusion.
deficiency is an issue of growing concern among many
scientists, due to changing lifestyle or cultural trends in which
many people around the world get less sun exposure and often
inadequate dietary levels of the vitamin.
It's a special problem with the elderly,
which often have reduced exposure to sunlight and less
ability to produce vitamin D in their skin – and at least partly as
a result, are more susceptible to bone fractures, chronic
inflammation and infectious disease.