Macrophage-specific MHCII expression is regulated by a remote Ciita enhancer controlled by NFAT5.
Macrophage-specific MHCII expression is regulated by a remote Ciita enhancer controlled by NFAT5.
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DOI：
10.1084/jem.20180314
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发表时间：
2018-11-05
期刊：
影响因子：
--
通讯作者：
López-Rodríguez C
中科院分区：
文献类型：
--
作者：
Buxadé M;Huerga Encabo H;Riera-Borrull M;Quintana-Gallardo L;López-Cotarelo P;Tellechea M;Martínez-Martínez S;Redondo JM;Martín-Caballero J;Flores JM;Bosch E;Rodríguez-Fernández JL;Aramburu J;López-Rodríguez C
NFAT 5通过远程增强子控制其共激活因子Ciita的转录来调节巨噬细胞MHCII表达。这种机制不同于以前在DC和B淋巴细胞中发现的机制，并将巨噬细胞与这些APC谱系区分开来。抗原呈递细胞（APC）中的MHCII是适应性免疫应答的关键调节因子。MHCII基因的表达由转录辅激活因子CIITA控制，CIITA本身通过细胞类型特异性启动子调节。在这里，我们表明，转录因子NFAT 5是需要表达的Ciita和MHCII在巨噬细胞，但不是在树突状细胞和其他APC。NFAT 5缺陷型巨噬细胞在CD4+ T淋巴细胞中表现出MHCII依赖性应答的缺陷性激活，并减弱了体内引起移植物排斥反应的能力。NFAT 5免疫沉淀染色质的超测序分析揭示了Ciita上游远端的NFAT 5调节区。该区域是CIITA和因此MHCII表达所需的，表现出活性增强子如H3K27乙酰化标记的NFAT 5依赖性特征，并且需要NFAT 5与CIITA髓样启动子I相互作用。我们的研究结果揭示了NFAT 5调节机制，维持CIITA和MHCII在巨噬细胞中的表达，从而调节它们的T淋巴细胞引发能力。
NFAT5 regulates macrophage MHCII expression by controlling the transcription of its coactivator Ciita through a remote enhancer. This mechanism differs from those previously found in DCs and B lymphocytes and distinguishes macrophages from these APC lineages. MHCII in antigen-presenting cells (APCs) is a key regulator of adaptive immune responses. Expression of MHCII genes is controlled by the transcription coactivator CIITA, itself regulated through cell type–specific promoters. Here we show that the transcription factor NFAT5 is needed for expression of Ciita and MHCII in macrophages, but not in dendritic cells and other APCs. NFAT5-deficient macrophages showed defective activation of MHCII-dependent responses in CD4+ T lymphocytes and attenuated capacity to elicit graft rejection in vivo. Ultrasequencing analysis of NFAT5-immunoprecipitated chromatin uncovered an NFAT5-regulated region distally upstream of Ciita. This region was required for CIITA and hence MHCII expression, exhibited NFAT5-dependent characteristics of active enhancers such as H3K27 acetylation marks, and required NFAT5 to interact with Ciita myeloid promoter I. Our results uncover an NFAT5-regulated mechanism that maintains CIITA and MHCII expression in macrophages and thus modulates their T lymphocyte priming capacity.
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DOI：
10.1073/pnas.1215934110
发表时间：
2013-10-01
影响因子：
11.1
作者：
Berga-Bolanos, Rosa;Alberdi, Maria;Lopez-Rodriguez, Cristina
通讯作者：
Lopez-Rodriguez, Cristina
影响因子：
30.5
作者：
Baroja-Mazo, Alberto;Martin-Sanchez, Fatima;Pelegrin, Pablo
通讯作者：
Pelegrin, Pablo
影响因子：
3
作者：
Clausen, BE;Burkhardt, C;Förster, I
通讯作者：
Förster, I
DOI：
10.1084/jem.20111569
发表时间：
2012-02-13
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Buxadé M;Lunazzi G;Minguillón J;Iborra S;Berga-Bolaños R;Del Val M;Aramburu J;López-Rodríguez C
通讯作者：
López-Rodríguez C
影响因子：
29
作者：
Jantsch J;Schatz V;Friedrich D;Schröder A;Kopp C;Siegert I;Maronna A;Wendelborn D;Linz P;Binger KJ;Gebhardt M;Heinig M;Neubert P;Fischer F;Teufel S;David JP;Neufert C;Cavallaro A;Rakova N;Küper C;Beck FX;Neuhofer W;Muller DN;Schuler G;Uder M;Bogdan C;Luft FC;Titze J
通讯作者：
Titze J