New role for immune cells in our gut

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.

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