心脏移植慢性排斥反应最终会引起心脏供体的纤维化和血管病变，导致超过50%的心脏供体在术后11年内出现失功。受体单核细胞来源的树突状细胞（mono-DCs）术后早期在供体内的免疫应答介导排斥反应，而现有的免疫抑制剂对这种先天性免疫细胞应答无效，这可能是导致慢性排斥反应的主要原因。我们的前期研究显示内源性IL-33可以限制mono-DCs在供体内的早期浸润，抑制小鼠心脏移植慢性排斥反应。而我们的预实验发现，含有全长内源性IL-33的细胞外基质囊泡（IL-33+MBV）在供体局部应用同样可以限制mono-DCs在供体内的早期免疫应答。因此，本项目拟通过体内外实验研究IL-33+MBV影响mono-DCs免疫应答的作用，明确其在小鼠心脏移植慢性排斥反应中的功能，揭示IL-33+MBV作用于mono-DCs，影响慢性排斥反应的作用机制，为IL-33+MBV作为新型免疫抑制剂的研发提供理论基础。

Chronic heart allograft rejection (CR) culminates in donor fibrosis and vasculopathy with a resultant loss of >50% of donors within 11 years post-transplantation. The immune responses of recipient monocyte-derived dendritic cells in donor induces the allograft rejection while available immunosuppressants are ineffective in preventing this innate immune cell response, which possibly play a key role in CR. Our previously studies show that endogenous IL-33 limits the infiltrating of mono-DCs into donor early after transplantation to protect against CR. What's more, our preliminary studies indicate that the IL-33 positive matrix bound nanovesicle (IL-33+MBV) with full-length endogenous IL-33 locally covering on donor could limit the early immune responses of recipient mono-DCs in donor. Therefore, in this project we attempt to study the impacts of IL-33+MBV on immune responses of recipient mono-DCs in vitro and vivo, and define the functions of IL-33+MBV to CR, and reveal the mechanisms of that IL-33+MBV effects on mono-DCs and then impacts to CR which may support IL-33+MBV as a novel immnuosuppressant.