Rare disease gives new insight into regulatory T cell function

Patients with the rare disease IPEX lack regulatory T cells and develop serious autoimmune diseases in which the immune system attacks the body's own tissue, such as type 1 diabetes, enteritis and dermatitis. In studies of 17 patients with IPEX, a research group at Karolinska Institutet has now been able to define which self-molecules are targeted by the immune system when regulatory T cells are lacking.

"Gut-related proteins were significantly over-represented amongst the target molecules we identified. We interpret this as regulatory T cells having a particularly important function in regulating the immune system in the gut," says corresponding author Daniel Eriksson, researcher at the Department of Medicine, Karolinska Institutet (Solna). "Our findings fit well with clinical presentation of the disease, in which symptoms from the gut dominate."

The researchers took advantage of a method that makes it possible to examine the immune response against 9,000 proteins in parallel.

"Our study is the first large-scale assay of how the immune system attacks the organs of IPEX patients," says Dr Eriksson.

Regulatory T cells have been called the "police" of the immune system, as they can prevent other immune cells from attacking the body's own tissues, discoveries that were awarded the 2017 Crafoord Prize.

“我们希望我们的结果将使它更容易iagnose patients with IPEX and monitor them during treatment," says Nils Landegren, researcher at the same department and the study's last author. "The next question is how understanding of regulatory T cell function can be used for developing new treatments for autoimmune diseases."

The study was conducted in close collaboration with numerous international researchers from Stanford University School of Medicine and elsewhere. It was financed by several bodies, including the Swedish Research Council, Region Stockholm, the Swedish Society for Medical Research (SSMF), the Crafoord foundation, and the Torsten and Ragnar Söderberg Foundation.