TLRs in the Gut. IV. Negative regulation of Toll-like receptors and intestinal homeostasis: addition by subtraction
TLRs in the Gut. IV. Negative regulation of Toll-like receptors and intestinal homeostasis: addition by subtraction
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DOI：
10.1152/ajpgi.00531.2006
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发表时间：
2007-06-01
影响因子：
4.5
通讯作者：
Podolsky, Daniel K.
中科院分区：
文献类型：
--
作者：
Shibolet, Oren;Podolsky, Daniel K.
Toll样受体（Toll like receptors，TLR）是一类识别微生物上保守分子基序的跨膜蛋白。配体与TLR的结合启动激活NF-κ B、MAPK和干扰素应答因子的信号级联。这些最终导致细胞应答，包括抗微生物杀伤机制的激活、细胞因子和趋化因子的产生、抗原呈递细胞的成熟和适应性免疫应答的募集。肠上皮细胞代表与细菌生物量直接接触而存在的独特细胞群体。TLR信号传导的启动受到严格调控，因为TLR的长期和过度活化可导致对宿主有害的不受控制的炎症。不同的机制似乎有助于控制肠上皮中TLR的激活。这些包括几种负调节剂的集体效应，包括IRAK-M，TOLLIP，SIGIRR，A20，Nod 2和PPAR γ。然而，仍有待确定它们是否包括阴性对照机制的整个谱，以及它们如何被绕过以在病原体挑战期间触发激活。
Toll-like receptors (TLRs) are a family of transmembrane proteins that recognize conserved molecular motifs on microorganisms. Ligand binding to TLRs initiates signaling cascades that activate NF-kappa B, MAPK, and interferon response factors. These culminate in cellular responses including activation of antimicrobial killing mechanisms, production of cytokines and chemokines, maturation of antigen presenting cells, and the recruitment of the adaptive immune response. Intestinal epithelial cells represent a unique population of cells that exist in direct contact with a biomass of bacteria. Initiation of TLR signaling is tightly regulated because prolonged and excessive activation of TLRs can lead to uncontrolled inflammation detrimental to the host. Varied mechanisms appear to contribute to control of TLR activation in the intestinal epithelium. These include the collective effects of several negative regulators that include IRAK-M, TOLLIP, SIGIRR, A20, Nod2, and PPAR gamma. However, it remains to be determined whether they comprise the entire spectrum of negative control mechanisms and how they are bypassed to trigger activation during challenge by pathogens.