Heme-mediated SPI-C induction promotes monocyte differentiation into iron-recycling macrophages.
Heme-mediated SPI-C induction promotes monocyte differentiation into iron-recycling macrophages.
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DOI：
10.1016/j.cell.2014.01.069
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发表时间：
2014-03-13
期刊：
影响因子：
64.5
通讯作者：
Murphy KM
中科院分区：
文献类型：
--
作者：
Haldar M;Kohyama M;So AY;Kc W;Wu X;Briseño CG;Satpathy AT;Kretzer NM;Arase H;Rajasekaran NS;Wang L;Egawa T;Igarashi K;Baltimore D;Murphy TL;Murphy KM
脾红髓巨噬细胞（RPM）降解衰老红细胞和循环血红素相关铁。转录因子Spic是由RPM选择性表达的，是它们发育所必需的，但诱导Spic的生理刺激尚不清楚。在这里，我们报道了Spic也调节F4/80+VCAM1+骨髓巨噬细胞（BMM）的发育，并且Spic在BMM和RPM发育中的表达是由血红素（红细胞降解的代谢物）诱导的。病理性溶血导致过量血红素导致RPM和BMM的丢失，但诱导单核细胞Spic产生新的RPM和BMM。Spic在单核细胞中的表达受到转录抑制因子Bach1的组构性抑制。血红素诱导蛋白酶体依赖性BACH1降解和快速Spic抑制。此外，BACH1中介导血红素依赖性降解的半胱氨酸-脯氨酸二肽基元是血红素诱导Spic所必需的。这些发现是代谢物驱动组织内巨噬细胞亚群分化的第一个例子，并为铁稳态提供了新的见解。
Splenic red pulp macrophages (RPM) degrade senescent erythrocytes and recycle heme-associated iron. The transcription factor Spic is selectively expressed by RPM and is required for their development, but the physiologic stimulus inducing Spic is unknown. Here, we report that Spic also regulated the development of F4/80+VCAM1+ bone marrow macrophages (BMM) and that Spic expression in BMM and RPM development was induced by heme, a metabolite of erythrocyte degradation. Pathologic hemolysis induced loss of RPM and BMM due to excess heme but induced Spic in monocytes to generate new RPM and BMM. Spic expression in monocytes was constitutively inhibited by the transcriptional repressor Bach1. Heme induced proteasome-dependent BACH1 degradation and rapid Spic derepression. Furthermore, cysteine-proline dipeptide motifs in BACH1 that mediate heme-dependent degradation were necessary for Spic induction by heme. These findings are the first example of metabolite-driven differentiation of a tissue-resident macrophage subset and provide new insights into iron homeostasis.
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影响因子：
82.9
作者：
通讯作者：
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DOI：
10.1038/nri2528
发表时间：
2009-04
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
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影响因子：
3.6
作者：
Beaumont, Carole;Delaby, Constance
通讯作者：
Delaby, Constance
影响因子：
6
作者：
Boyle, Joseph J.;Harrington, Heather A.;Haskard, Dorian O.
通讯作者：
Haskard, Dorian O.
DOI：
10.1038/nri3073
发表时间：
2011-10-14
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
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