Characterization of leucocyte subsets induced by Interleukin 11, including the expansion and activation of myeloid-derived suppressor cells and their role in the pathogenesis of inflammatory bowel disease

• Applicant: Professor Dr. Jan Däbritz
• Subject Area: Pediatric and Adolescent Medicine
• Term: from 2012 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 218589945

Myeloid-derived suppressor cells (MDSCs) are one of the main cell populations responsible for regulating immune responses. MDSCs accumulate during tumor progression, autoimmunity, chronic infection and other pathological conditions, and can potently suppress T-cell function. Recently, MDSCs have been suggested as a new immunoregulatory pathway in the pathogenesis of inflammatory bowel diseases (IBD). However, the underlying mechanisms for activation of MDSCs are currently not well defined. The MDSC population is influenced by several different factors including cytokines. Interleukin 11 (IL-11) has been shown to play a regulatory role in animal models of colitis, but the influence of IL-11 on MDSCs has not been investigated so far. Thus, the overall aim of this project is the examination of the potential of IL-11 to induce MDSCs, characterization of the IL-11 induced MDSCs phenotype, investigation of the mechanisms of expansion and suppressive functions of IL-11 induced MDSCs as well as the potential to target these cells for therapeutic benefit in IBD using various mouse models of intestinal inflammation. This project is likely to reveal novel insights into the pathogenesis of IBD, and to identify mechanisms by which modulation of immunity may alter the natural history of this disease, thereby underpinning development of new therapeutic options.

• DFG Programme: Research Fellowships
• International Connection: Australia
• Host: Professor Dr. Andrew S. Giraud