雌激素通过调节IRF4促进巨噬细胞向M2型极化

Estrogen promotes M2 macrophages polarization by increasing IRF4 expression

病毒性心肌炎、系统性红斑狼疮及肝癌等多种疾病其发病及严重情况呈现明显的性别差异,其中巨噬细胞不同极化是引起上述差异的重要原因。目前发现,雌激素(estrogen)可显著影响巨噬细胞极化,然而其涉及的分子免疫学机制尚不明了。本研究我们探讨了雌激素对骨髓来源巨噬细胞(BMM)极化的影响极其分子机制。雌激素虽不影响巨噬细胞的分化,但可显著促进巨噬细胞向M2型极化。进一步研究发现雌激素可上调M2型巨噬细胞重要转录因子IRF4的表达,且上调水平与M2极化程度呈正相关。提示,雌激素通过上调转录因子IRF4进而促进了M2型巨噬细胞极化。本研究为雌雄小鼠对疾病发病敏感差异性作出了一定理论解释,同时为通过调控巨噬细胞极化治疗疾病提供了新的线索。

Differential macrophage polarization in male and female mice defines susceptibility to disease. It is reported that estrogen plays an important role in macrophage polarization, but its underlying molecular mechanism is still unknown. In this study we studied the effect of estrogen on polarization of the M-CSF-induced bone marrow macrophages and then explored its potential mechanisms. We found that estrogen did not affect macrophage differentiation but promoted M2 polarization . Further, we found that estrogen could increase expression of M2-associated transcription factor IRF4. More importantly, the level of IRF4 was correlated with the extent of estrogen-induced M2 polarization. This study may provide some explanation for difference in susceptibility to diseases between male and female mice, and may also provide new clues for macrophage polariza- tion-based treatements.