我们发现，在树突状细胞（DC）分化培养系统中，甘露聚糖结合凝集素（MBL）可抑制单核细胞（Mo）向DC分化而诱生CD11b+ CD14+ CD33+ HLA-DRlow、抑制T细胞功能的Mo型髓源抑制细胞（M-MDSC）。据此提出本项目，拟对MBL诱导M-MDSC发育及在类风湿关节炎（RA）的意义进行以下研究：①体外：细胞表型、功能及机制；②临床：MBL与M-MDSC及RA病情的关系；③动物模型：胶原诱导关节炎小鼠MBL与M-MDSC及病变的关系、补充MBL/过继M-MDSC的影响。创新点和意义有：①提出MBL通过调控M-MDSC发育参与免疫调节的新观点，将丰富天然免疫指导获得性免疫的基础理论。②从免疫调节紊乱新角度阐述MBL失衡有关疾病发病机制，为其治疗研究提供新的科学依据。③揭示MBL失衡—M-MDSC紊乱—RA病变的关系，为靶向MBL调控M-MDSC发育以治疗RA提供理论和实验依据。

We recently found that mannan-binding lectin (MBL) inhibited the differentiation of monocytes (Mos) into dendritic cells (DCs) in a DC-inducing culture system, but induced Mos to differentiate into myeloid derived suppressor cells (M-MDSCs) characterized by CD11b+ CD14+ CD33+ HLA-DRlow, high expresions of interleukin-10 and -6 and capable of inhibiting proliferation of, and IFN-γ production by autologous T cells. On the basis of these findings, we propose the present grant. The effects of MBL on M-MDSC development processes, including their phenotype, functional capacity and the mechanisms underlining these effects such as the relative signal pathways of M-MDSC development, will be studied. The level of MBL and the frequency and competence of M-MDSCs in blood or lymphoid tissues will be examined, and the association among MBL level, M-MDSCs’ frequency and competence, disease severity and tissue inflammation will be analyzed in patients with rheumatoid arthritis (RA) or in collagen-induced arthritis (CIA) mice. The features of MDSCs and the disease pathology in CIA mice will be also examined by MBL reconstitution or adoptive transfer of MDSCs. The innovation points and the significance of this project lie in: first, the viewpoint that MBL has a hand in acquired immune responses through regulating the development of M-MDSCS will be put forward, which will enrich the basic theory that innate immune system instructs acquired immune responses, and provide new theoretical bases and targets for treatment of diseases resulted from MBL imbalance and M-MDSC function disorder. Second, the pathogenesis mechanisms of MBL unbalance (deficiency or hyperfunction) will be expounded from a new viewpoint of immunoregulation disorder, which may supply new bases and strategies for treatment of this kind of diseases. Third, the relationship among MBL unbalance, M-MDSC disorder and RA disease severity will be revealed, which may help to elucidate the pathogenesis of RA and to develop novel strategies for RA therapies.