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

髓系抑制细胞(MDSCs)是调节免疫反应的主要细胞群之一。MDSCs在肿瘤进展、自身免疫、慢性感染等病理条件下积聚，能有效抑制T细胞功能。近年来，MDSCs被认为是炎症性肠病(IBD)发病机制中的一条新的免疫调节途径。然而，MDSCs激活的潜在机制目前还没有很好的定义。MDSC群体受到几种不同因素的影响，包括细胞因子。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，但迄今尚未研究IL-11对MDSCs的影响。因此，本项目的总体目标是检测IL-11诱导MDSCs的潜力，鉴定IL-11诱导的MDSCs的表型，研究IL-11诱导的MDSCs的扩增和抑制功能的机制，以及利用不同的小鼠肠道炎症模型来靶向这些细胞治疗IBD的可能性。该项目可能揭示对IBD发病机制的新见解，并确定免疫调节可能改变这种疾病的自然历史的机制，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.