Regulatory T-cells in the celiac intestinal mucosa: a new perspective for treatment?

In the physiological condition, the immune system tolerizes the huge amount of proteins that are daily introduced into the gastro-intestinal tract with the diet, a phenomenon known as oral tolerance. Many and complex immunological mechanisms are involved in the induction of oral tolerance including suppression by regulatory T cells (Treg). In addition, a key role in the gut homoeostasis is sustained by immunosuppressive cytokines, such as interleukin (IL)-10 and transforming growth factor (TGF) , released by Treg. Coeliac disease is a common, and almost worldwide spread, intolerance to wheat gluten and related proteins from barley and rye. Coeliac disease is caused by abnormal pro-inflammatory responses to ingested gluten in which gliadin-reactive T cells are one of the main actors in orchestrating the complex adverse immune reactions following gluten ingestion. Our recent studies have revealed that the treatment with IL-10 of small-intestinal mucosa from coeliac disease patients in remission prevents the massive immune activation induced by gluten challenge. Furthermore, we have observed that coeliac intestinal mucosa harbours a subset of Treg, the Tr1, that through the release of both IL-10 and TGF- inhibit the pathogenic response to in vitro gluten challenge. Herein we discuss these recent studies on Treg in coeliac disease mucosa and envision an IL-10-based therapeutic approach for coeliac disease.