Identification and characterization of a unique leucine-rich repeat protein (LRRC33) that inhibits Toll-like receptor-mediated NF-κB activation
Identification and characterization of a unique leucine-rich repeat protein (LRRC33) that inhibits Toll-like receptor-mediated NF-κB activation
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DOI：
10.1016/j.bbrc.2013.03.071
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发表时间：
2013-04-26
影响因子：
3.1
通讯作者：
Yang, Rongcun
中科院分区：
文献类型：
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作者：
Liu, Jingyi;Zhang, Zhujun;Yang, Rongcun
Toll 样受体 (TLR) 是针对病毒、细胞内细菌或寄生虫等病原微生物的先天免疫反应的重要启动子。尽管先天免疫系统旨在对抗传染性病原体，但 TLR 信号传导的过度激活可能会导致不必要的炎症，从而产生危险后果。抑制过度炎症和控制先天免疫稳态的机制是深入研究的焦点。在这里，我们证明了 LRRC33 是富含亮氨酸重复序列 (LRR) 蛋白家族的新成员，在 TLR 信号转导脱敏中发挥着关键作用。 LRRC33 是 TLR 同源物，在细胞外区域包含 17 个假定的 LRR，但缺乏细胞质 Toll/IL-1 受体 (TIR) 结构域。 LRRC33 的表达似乎无处不在，在骨髓、胸腺、肝脏、肺、肠和脾中发现高水平表达。 LRRC33 的 LRR 是与 TLR 相互作用及其对 NF-κ B 和 AP-1 激活以及细胞因子产生的抑制作用所必需的。我们的研究为发育和人类疾病中的 TLR 信号传导和炎症反应提供了新的见解。 (C) 2013 Elsevier Inc. 保留所有权利。
Toll-like receptors (TLRs) are important initiators in innate immune responses against pathogenic microbes such as viruses, intracellular bacteria or parasites. Although the innate immune system is designed to fight infectious pathogens, excessive activation of TLR signaling may lead to unwarranted inflammation with hazardous outcomes. Mechanisms of restraining excessive inflammation and controlling homeostasis for innate immunity are the focus of intense study. Here we showed that LRRC33, a novel member of leucine-rich repeat (LRR) protein family, plays a critical role in desensitizing TLR signaling. LRRC33 is TLR homolog that contains 17 putative LRRs in the extracellular region but lacks a cytoplasmic Toll/IL-1 receptor (TIR) domain. Expression of LRRC33 appears to be ubiquitous with high level of expression found in bone marrow, thymus, liver, lung, intestine and spleen. The LRRs of LRRC33 is required for the interaction with TLR and its inhibitory effect on NF-kappa B and AP-1 activation as well as cytokine production. Our study sheds new insight into the TLR signaling and inflammatory response in development and human diseases. (C) 2013 Elsevier Inc. All rights reserved.