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

髓源性抑制细胞（MDSCs）是负责调节免疫反应的主要细胞群之一。MDSCs在肿瘤进展、自身免疫、慢性感染和其他病理条件下积累，并能有效抑制t细胞功能。近年来，MDSCs被认为是炎症性肠病（IBD）发病机制中的一种新的免疫调节途径。然而，MDSCs激活的潜在机制目前尚未明确。MDSC群体受包括细胞因子在内的几个不同因素的影响。白细胞介素11 （IL-11）已被证明在结肠炎动物模型中发挥调节作用，但IL-11对MDSCs的影响迄今尚未被研究。因此，本项目的总体目标是研究IL-11诱导MDSCs的潜力，表征IL-11诱导MDSCs的表型，研究IL-11诱导MDSCs的扩张和抑制功能的机制，以及利用各种肠道炎症小鼠模型靶向这些细胞治疗IBD的潜力。该项目可能会揭示IBD发病机制的新见解，并确定免疫调节可能改变该疾病自然史的机制，从而为开发新的治疗方案奠定基础。

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.