巨噬细胞极化被认为在慢性肝炎导致的纤维化进展中发挥重要作用，但介导其极化的关键因子及信号通路尚不完全清楚，肝纤维化难以实现精准治疗。我们前期发现，小鼠肝脏巨噬细胞在白介素37（IL-37）作用下发生M2型极化，而M2型巨噬细胞与器官纤维化高度相关。IL-37是新发现的免疫因子，可结合巨噬细胞表面特异性受体IL-1R8转导细胞信号，故推测IL-37/IL-1R8通路在巨噬细胞极化中发挥重要作用，并对肝纤维化进程产生影响。本研究拟利用细胞生物学和免疫学实验方法对该假设进行证明：构建肝纤维化小鼠模型，以明确IL-37在肝纤维化进展中的作用；进一步通过分析IL-37/IL-1R8通路介导的巨噬细胞极化分子机制及其对肝星状细胞激活、细胞外基质沉积的影响，来证明巨噬细胞IL-37/IL-1R8通路在肝纤维化形成中的重要作用。本研究为设计以调节巨噬细胞极化为作用机理的抗纤维化精准治疗方案提供理论基础。

Macrophage polarization is considered to play an important role in fibrosis caused by chronic hepatitis. But as the key factor and the signaling pathway in regulating polarization are not fully understood, the accurate treatment for liver fibrosis has not been realized. In preliminary study, we have found that the mouse liver macrophages had an M2 polarization under the treatment of interleukin-37 (IL-37), and the M2 macrophages were highly correlated with organ fibrosis. IL – 37, a new immune factor, could interact with the macrophages cell specific surface receptor IL-1R8 for signal transduction. So we speculated IL-37/IL-1R8 pathway played the important role in the macrophage polarization, which make key effect on liver fibrosis development. In this study, the experimental methods of cell biology and immunology are used to prove the above hypothesis. The mouse model of hepatic fibrosis will be constructed to clarify the role of IL-37 in the progression of hepatic fibrosis; Further, the molecular mechanism of IL-37/IL-1R8 pathway mediated macrophage polarization and its effect on activation of hepatic stellate cells and extracellular matrix deposition are going to be analyzed, to prove macrophage IL-37/IL–1R8 pathway is a key regulator of liver fibrosis. This study provides a theoretical basis for designing of an anti-fibrotic precision treatment program that aiming for modulating the macrophage polarization.