脓毒症是病原微生物入侵机体后所致的全身炎症反应综合症。M2型巨噬细胞在下调炎症反应，促进组织修复中发挥重要作用。S1PR3参与调节M2型巨噬细胞向炎症病灶募集，维持机体免疫稳态。我们前期研究发现：S1PR3促进巨噬细胞募集，减轻脏器损伤，对脓毒症产生保护作用。文献报道趋化因子CX3CL1是介导血液中抗炎单核细胞向组织募集，并转变为M2型巨噬细胞的关键分子。因此，我们推测：S1PR3通过调节CX3CL1的表达，调控M2型巨噬细胞募集，介导脓毒症发生发展。本项目拟从整体、细胞和分子水平，观察S1PR3对脓毒症M2型巨噬细胞的募集作用；明确S1PR3通过上调CX3CL1表达促进血液抗炎单核细胞向组织募集并转化为M2型巨噬细胞，参与脓毒症发生发展；深入探讨S1PR3调控M2型巨噬细胞募集的分子机制，为脓毒症免疫防治提供新思路。

Sepsis is recast as a systemic inflammatory response syndrome and assumed to be the result of the host’s invasion by pathogenic organisms. M2 macrophages contribute to alleviate inflammatory response and promote tissue repair during sepsis. S1PR3 regulates recruitment of M2 macrophage to inflammatory lesions, keeping the balance of the body’s immune system. In our pilot study, it was demonstrated that S1PR3 protected mice from sepsis by promoting macrophage recruitment and alleviating tissue damage. Chemokine CX3CL1 facilitates the accumulation of the anti-inflammatory monocytes in diverse tissues, which are the most important source of M2 macrophage. Therefore, we hypothesis that S1PR3 will be involved in the pathogenesis of sepsis via modulating the CX3CL1 expression and subsequent recruitment of M2 macrophage. The present project will, from the systemic, cellular and molecular levels, analyze the function of S1PR3 in M2 macrophage recruitment, to clarify the roles of S1PR3 in up-regulating CX3CL1 expression and subsequent tissue recruitment of anti-inflammatory monocytes during sepsis, and further to explore the signal pathway how S1PR3 mediates the tissue recruitment of M2 macrophage. This study will provide new ideas and targets in the prevention and management of sepsis.