【进展|热点】BLOOD: 雌激素受体通过上调IRF4促进DC的分化
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Estrogen receptor signaling promotes dendritic cell differentiation by increasing expression of the transcription factor IRF4
Blood, 14 January 2010, Vol. 115, No. 2, pp. 238-246.
During inflammation, elevated granulocyte macrophage–colony-stimulating factor (GM-CSF) directs the development of new dendritic cells (DCs). This pathway is influenced by environmental factors, and we previously showed that physiologic levels of estradiol, acting through estrogen receptor alpha (ER), promote the GM-CSF–mediated differentiation of a CD11b+ DC subset from myeloid progenitors (MPs). We now have identified interferon regulatory factor 4 (IRF4), a transcription factor induced by GM-CSF and critical for CD11b+ DC development in vivo, as a target of ER signaling during this process. In MPs, ER potentiates and sustains GM-CSF induction of IRF4. Furthermore, retroviral delivery of the Irf4 cDNA to undifferentiated ER–/– bone marrow cells restored the development of the estradiol/ER-dependent DC population, indicating that an elevated amount of IRF4 protein substitutes for ER signaling. Thus at an early stage in the MP response to GM-CSF, ER signaling induces an elevated amount of IRF4, which leads to a developmental program underlying CD11b+ DC differentiation.
在炎症过程中生理水平的雌二醇可以通过雌激素受体(ER)来促进GM-CSF介导的DC的分化和成熟,但是具体机理不明,此文通过研究发现estradiol-ER是通过IRF4来发挥作用,并且通过体外试验和knockout模型阐述了其中的机理。
不知道estradiol-ER对于DC细胞的作用是不是可以部分解释男女免疫系统的差异,那么反过来雄激素对于DC是否有类似的作用,或者是反作用呢?
通过E2处理,MHCII+DC的表达变化。

Blood, 14 January 2010, Vol. 115, No. 2, pp. 238-246.
During inflammation, elevated granulocyte macrophage–colony-stimulating factor (GM-CSF) directs the development of new dendritic cells (DCs). This pathway is influenced by environmental factors, and we previously showed that physiologic levels of estradiol, acting through estrogen receptor alpha (ER), promote the GM-CSF–mediated differentiation of a CD11b+ DC subset from myeloid progenitors (MPs). We now have identified interferon regulatory factor 4 (IRF4), a transcription factor induced by GM-CSF and critical for CD11b+ DC development in vivo, as a target of ER signaling during this process. In MPs, ER potentiates and sustains GM-CSF induction of IRF4. Furthermore, retroviral delivery of the Irf4 cDNA to undifferentiated ER–/– bone marrow cells restored the development of the estradiol/ER-dependent DC population, indicating that an elevated amount of IRF4 protein substitutes for ER signaling. Thus at an early stage in the MP response to GM-CSF, ER signaling induces an elevated amount of IRF4, which leads to a developmental program underlying CD11b+ DC differentiation.
在炎症过程中生理水平的雌二醇可以通过雌激素受体(ER)来促进GM-CSF介导的DC的分化和成熟,但是具体机理不明,此文通过研究发现estradiol-ER是通过IRF4来发挥作用,并且通过体外试验和knockout模型阐述了其中的机理。
不知道estradiol-ER对于DC细胞的作用是不是可以部分解释男女免疫系统的差异,那么反过来雄激素对于DC是否有类似的作用,或者是反作用呢?
通过E2处理,MHCII+DC的表达变化。
