Mφ是一群在免疫应答中发挥重要作用的高度异质性细胞群体，其功能的改变或缺失与特定组织部位炎症疾病的发生密切相关，对Mφ极化研究已成为备受关注的焦点。我们前期研究发现中和EAM小鼠HMGB1能够减少单核-Mφ浸润、分化，抑制其向M1极化，极化过程中HMGB1的表达发生改变；报道显示M1细胞分泌IL-23。因此，提出HMGB1调控Mφ极化参与了Th17介导的EAM发生的假说。为证明以上假说本课题拟从体内外两方面进行：体外研究HMGB1调节Mφ极化的分子机制以及极化的M1对Th17增殖、分化、凋亡的影响；体内通过CD11b-DTR转基因小鼠构建、携带HMGB1siRNA多功能聚合微球颗粒的靶向干预以及抗HMGB1抗体的干预，进一步阐明HMGB1调控单核-巨噬细胞分化、极化参与Th17介导的EAM发生的分子机制，为开展以HMGB1为靶向的炎症性疾病的免疫干预治疗提供理论依据。

Macrophage, a highly heterogeneous cell population, plays an important role in the immune response. Its function changes or deficiency were associated with many inflammatory diseases. Recently, many works focused on macrophages polarization. Our previous works showed that blockade HMGB1 could reduce infiltration, differentiation of monocyte-macrophage, inhibit its’ polarization to M1 and HMGB1 expression changed during monocytes-macrophage differentiation and polarization. Furthermore, polarized M1 could secrete IL-23. Therefore, we speculated that HMGB1 involved in the EAM pathogenesis mediated by Th17 cell via controlling monocytes-macrophage differentiation and polarization. To prove the hypothesis, in vitro, two projects were carried out, one is to explore the mechanism of HMGB1 modulating monocyte-macrophage differentiation and polarization, the other was to make clear the function of polarized M1 contributing Th17 cells expansion (such as proliferation, differentiation, apoptosis) ; in vivo,CD11b-DTR transgenic mice construction, multifunctional polymeric microsphere particles carrying HMGB1 siRNA targeted monocyte-macrophage and anti-HMGB1 antibodies intervention were used to further clarify the mechanism of HMGB1 regulation monocytes-macrophage differentiation and polarization in Th17-mediated EAM model. All the data will provide the basis for immune intervention therapy targeted HMGB1 of inflammatory diseases.