The role of suppression of tumorigenicity 2 (ST2) expressing regulatory T cells in intestinal inflammation and colitis-associated colon cancer

• Applicant: Dr. Eva Pastille
• Subject Area: Gastroenterology ; Immunology
• Term: from 2017 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 387232980

Summary:Patients suffering from inflammatory bowel disease (IBD) like ulcerative colitis or Crohn´s disease bear an elevated risk of colorectal cancer. The underlining immunological mechanisms are not well understood. Regulatory T cells (Tregs) display a central part of the gut mucosal immune system as they are able to suppress inflammatory responses and thereby maintain intestinal homeostasis. Besides their protective effects on intestinal inflammation, during tumourigenesis Tregs are well known to impair anti-tumour immune responses. In the murine Azoxymethane (AOM) /Dextran sulphate sodium (DSS) model we could demonstrate the importance of Tregs in the induction and progression of colitis-associated colon cancer (CAC). In further studies we observed an increase of IL-33 expression and an accumulation of CD4+ Foxp3+ ST2+ Tregs in the colon of mice suffering from CAC. Moreover, ST2 deficient mice which were subjected to the AOM/DSS protocol showed a reduced tumour development and lower frequencies of CD4+ Foxp3+ Tregs in the colon compared to AOM/DSS treated wildtyp control animals. However, in the context of CAC it remains to be defined how intestinal expression of IL-33 might modulate the anti-tumour immune response and how it might control the function of Tregs through ST2. Therefore the detailed analysis of IL-33 and ST2 expressing Tregs during chronic colitis and tumourigenesis will be the objective of this project. The results achieved from this will provide new targets for the directed immunological manipulation of Tregs during chronic colitis and tumourigenesis.

• DFG Programme: Research Grants