NF-κB 在 T 细胞选择中的复杂作用。
The complicated role of NF-kappaB in T-cell selection.
机构信息
CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences (CAS), Beijing, China.
出版信息
Cell Mol Immunol. 2010 Mar;7(2):89-93. doi: 10.1038/cmi.2009.112.
Abstract
The nuclear factor (NF)-kappaB transcription factor family plays important roles in the immune system. Aberrant NF-kappaB signaling is frequently associated with inflammation and autoimmune diseases but the underlying mechanisms are not fully understood. Recent studies show that NF-kappaB plays a critical role in T-cell central tolerance. Two NF-kappaB signaling pathways have been identified: the canonical pathway and the alternative pathway. In the establishment of T-cell central tolerance, the alternative pathway appears to be the key signaling component in thymic stromal cells for their development and function, while the canonical pathway exerts its function more in autonomous T-cell selection. This review intends to summarize the current understanding of the role of NF-kappaB in establishing T-cell central tolerance and highlight unsolved intriguing questions for future work.
摘要
核因子（NF）-κB 转录因子家族在免疫系统中发挥重要作用。异常的 NF-κB 信号与炎症和自身免疫性疾病密切相关，但其中的机制尚不完全清楚。最近的研究表明，NF-κB 在 T 细胞中枢耐受中起着关键作用。已经确定了两种 NF-κB 信号通路：经典途径和替代途径。在 T 细胞中枢耐受的建立中，替代途径似乎是胸腺基质细胞发育和功能所必需的关键信号成分，而经典途径在自主 T 细胞选择中发挥作用。本文旨在总结 NF-κB 在建立 T 细胞中枢耐受中的作用的最新认识，并强调未来工作中仍存在一些引人关注的问题。
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本文引用的文献
1
The impact of negative selection on thymocyte migration in the medulla.阴性选择对髓质中胸腺细胞迁移的影响。
Nat Immunol. 2009 Aug;10(8):823-30. doi: 10.1038/ni.1761. Epub 2009 Jun 21.
2
The cytokine RANKL produced by positively selected thymocytes fosters medullary thymic epithelial cells that express autoimmune regulator.由阳性选择的胸腺细胞产生的细胞因子RANKL促进表达自身免疫调节因子的髓质胸腺上皮细胞的生长。
Immunity. 2008 Sep 19;29(3):438-50. doi: 10.1016/j.immuni.2008.06.018.
3
The tumor necrosis factor family receptors RANK and CD40 cooperatively establish the thymic medullary microenvironment and self-tolerance.肿瘤坏死因子家族受体RANK和CD40协同建立胸腺髓质微环境和自身耐受性。
Immunity. 2008 Sep 19;29(3):423-37. doi: 10.1016/j.immuni.2008.06.015.
4
Generation and activation of multiple dimeric transcription factors within the NF-kappaB signaling system.核因子-κB信号系统内多种二聚体转录因子的产生与激活。
Mol Cell Biol. 2008 May;28(10):3139-50. doi: 10.1128/MCB.01469-07. Epub 2008 Feb 25.
5
Activation of cortical and inhibited differentiation of medullary epithelial cells in the thymus of lymphotoxin-beta receptor-deficient mice: an ultrastructural study.淋巴毒素-β受体缺陷小鼠胸腺中皮质激活及髓质上皮细胞分化受抑制：一项超微结构研究
J Anat. 2008 Feb;212(2):114-24. doi: 10.1111/j.1469-7580.2007.00851.x. Epub 2008 Jan 9.
6
Lymphotoxin beta receptor is required for the migration and selection of autoreactive T cells in thymic medulla.淋巴毒素β受体是胸腺髓质中自身反应性T细胞迁移和选择所必需的。
J Immunol. 2007 Dec 15;179(12):8069-75. doi: 10.4049/jimmunol.179.12.8069.
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Lymphotoxin pathway and Aire influences on thymic medullary epithelial cells are unconnected.淋巴毒素途径与自身免疫调节因子对胸腺髓质上皮细胞的影响并无关联。
J Immunol. 2007 Nov 1;179(9):5693-700. doi: 10.4049/jimmunol.179.9.5693.
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Blood. 2007 Dec 15;110(13):4351-9. doi: 10.1182/blood-2007-01-070284. Epub 2007 Sep 4.
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RANK signals from CD4(+)3(-) inducer cells regulate development of Aire-expressing epithelial cells in the thymic medulla.来自CD4(+)3(-)诱导细胞的RANK信号调节胸腺髓质中表达艾里蛋白的上皮细胞的发育。
J Exp Med. 2007 Jun 11;204(6):1267-72. doi: 10.1084/jem.20062497. Epub 2007 May 14.
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