The Transcription Factor ZEB2 Is Required to Maintain the Tissue-Specific Identities of Macrophages.
The Transcription Factor ZEB2 Is Required to Maintain the Tissue-Specific Identities of Macrophages.
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转录因子ZEB2是维持巨噬细胞组织特异性所必需的。
DOI：
10.1016/j.immuni.2018.07.004
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发表时间：
2018-08-21
期刊：
影响因子：
32.4
通讯作者：
Guilliams M
中科院分区：
文献类型：
--
作者：
Scott CL;T'Jonck W;Martens L;Todorov H;Sichien D;Soen B;Bonnardel J;De Prijck S;Vandamme N;Cannoodt R;Saelens W;Vanneste B;Toussaint W;De Bleser P;Takahashi N;Vandenabeele P;Henri S;Pridans C;Hume DA;Lambrecht BN;De Baetselier P;Milling SWF;Van Ginderachter JA;Malissen B;Berx G;Beschin A;Saeys Y;Guilliams M
不同巨噬细胞群体之间的异质性已经成为该谱系的定义特征。然而，定义巨噬细胞的保守因子在很大程度上仍然未知。转录因子ZEB 2最好描述其在上皮向间充质转化中的作用;然而，其在免疫系统中的作用现在才被阐明。我们在这里表明，Zeb 2表达是巨噬细胞的保守特征。使用Clec 4f-cre，Itgax-cre和Fcgr 1-cre小鼠靶向五种不同的巨噬细胞群体，我们发现ZEB 2的缺失导致巨噬细胞从组织中消失，再加上随后从开放龛中的骨髓前体中补充。从机制上讲，我们发现ZEB 2的功能是维持巨噬细胞的组织特异性身份。在库普弗细胞中，ZEB 2通过调节转录因子LXRα的表达来实现这一点，去除LXR α会重演库普弗细胞身份的丧失和消失。因此，巨噬细胞中需要ZEB 2表达以保持其组织特异性身份。ZEB 2在整个巨噬细胞谱系中高度表达ZEB 2保留了整个组织中巨噬细胞的组织特异性身份ZEB 2缺陷型巨噬细胞被WT对应物竞争，LXRα对库普弗细胞身份至关重要，并由ZEB 2 Scott et al.证明ZEB 2对于维持巨噬细胞的组织特性至关重要。ZEB 2的缺失导致不同巨噬细胞群体的组织特异性变化及其随后的消失。在库普弗细胞中，ZEB 2维持LXRα表达，LXR α表达的缺失再现了库普弗细胞身份的变化和它们的消失。
Heterogeneity between different macrophage populations has become a defining feature of this lineage. However, the conserved factors defining macrophages remain largely unknown. The transcription factor ZEB2 is best described for its role in epithelial to mesenchymal transition; however, its role within the immune system is only now being elucidated. We show here that Zeb2 expression is a conserved feature of macrophages. Using Clec4f-cre, Itgax-cre, and Fcgr1-cre mice to target five different macrophage populations, we found that loss of ZEB2 resulted in macrophage disappearance from the tissues, coupled with their subsequent replenishment from bone-marrow precursors in open niches. Mechanistically, we found that ZEB2 functioned to maintain the tissue-specific identities of macrophages. In Kupffer cells, ZEB2 achieved this by regulating expression of the transcription factor LXRα, removal of which recapitulated the loss of Kupffer cell identity and disappearance. Thus, ZEB2 expression is required in macrophages to preserve their tissue-specific identities. ZEB2 is highly expressed across the macrophage lineage ZEB2 preserves the tissue-specific identities of macrophages across tissues ZEB2 deficient macrophages are outcompeted by WT counterparts LXRα is crucial for Kupffer cell identity and is maintained by ZEB2 Scott et al. demonstrate that ZEB2 is critical for maintaining the tissue identities of macrophages. Loss of ZEB2 results in tissue-specific changes in different macrophage populations and their subsequent disappearance. In Kupffer cells, ZEB2 maintains LXRα expression, loss of which reproduces the change in Kupffer cell identity and their disappearance.
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DOI：
10.1084/jem.20150194
发表时间：
2015-11-16
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Omilusik KD;Best JA;Yu B;Goossens S;Weidemann A;Nguyen JV;Seuntjens E;Stryjewska A;Zweier C;Roychoudhuri R;Gattinoni L;Bird LM;Higashi Y;Kondoh H;Huylebroeck D;Haigh J;Goldrath AW
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DOI：
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发表时间：
2007-07-09
期刊：
The Journal of experimental medicine
影响因子：
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作者：
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通讯作者：
Reizis B
影响因子：
30.5
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影响因子：
64.5
作者：
Gosselin D;Link VM;Romanoski CE;Fonseca GJ;Eichenfield DZ;Spann NJ;Stender JD;Chun HB;Garner H;Geissmann F;Glass CK
通讯作者：
Glass CK
影响因子：
32.4
作者：
Guilliams M;Dutertre CA;Scott CL;McGovern N;Sichien D;Chakarov S;Van Gassen S;Chen J;Poidinger M;De Prijck S;Tavernier SJ;Low I;Irac SE;Mattar CN;Sumatoh HR;Low GHL;Chung TJK;Chan DKH;Tan KK;Hon TLK;Fossum E;Bogen B;Choolani M;Chan JKY;Larbi A;Luche H;Henri S;Saeys Y;Newell EW;Lambrecht BN;Malissen B;Ginhoux F
通讯作者：
Ginhoux F