Researchers have discovered a new role for immune cells called
Th17 cells in our intestines - they help to induce a particular
type of antibody, called immunoglobulin A (IgA), to fight
infections and toxins.
Until now, the main function of intestinal Th17 cells was
thought to be in helping provide a barrier to keep healthy bacteria
in our gut where they belong and prevent them moving out of the gut
and causing infections and cancer.
Gitta Stockinger's team at the Medical Research Council's
National Institute for Medical Research (NIMR; now part of
the Francis Crick Institute) studied mice with altered
genomes and discovered that Th17 cells can change their function
depending on their environment. The NIMR scientists worked with
colleagues from the Instituto Gulbenkian de Ciência in Oeiras,
Portugal and the University Medical Centre Hamburg-Eppendorf in
Germany.
There are structures in the intestine called Peyer's patches
which contain cells that protect us against toxins that can cause
disease. When such a threat is encountered, it stimulates the
production of antibodies by disease-fighting white blood
cells.
Dr Stockinger and her team discovered that when Th17 cells enter
Peyer's patches, they can change from their usual role in providing
a barrier function and instead start inducing
antibodies.
Dr Stockinger explained: "Previously it was shown that the
proteins released by Th17 cells support the barrier function of the
cells lining the intestine, which protect the body from contact
with the multitude of bacteria that live
there.
"However, in this paper we show that Th17 cells that enter
Peyer's patches alter their function to that of a type of immune
cells that support the production IgA antibodies by white blood
cells. IgA is very important for neutralising toxins that enter the
intestinal tract."
The researchers confirmed their findings by breeding mice that
failed to develop Th17 cells and challenging them with the toxin
that causes cholera. The mice failed to generate IgA in response to
the cholera toxin.
Dr Stockinger concluded: "Th17 cells play a role in various
autoimmune and inflammatory disorders - such as multiple sclerosis,
psoriasis and rheumatoid arthritis. This makes them an obvious
target for disease treatments. Antibodies directed at one of the
proteins produced by TH17 cells show high success rates in the
treatment of psoriasis, and other treatments that would target the
Th17 pathway are also being discussed as potential
therapies.
"However, such treatments would have to be carefully balanced so
that they did not adversely affect the Th17 cells that play an
essential barrier role in keeping the balance of healthy bacteria
in the gut."
The paper, TH17 cell plasticity in Peyer's patches is
responsible for induction of T cell dependent IgA
responses, was published in Nature
Immunology.