清道夫受體（Scavenger receptor, SR）是模式識(shí)別受體家族的重要成員,，具有廣泛的免疫生物學(xué)功能并參與多種疾病的發(fā)生，其中對(duì)SR在炎癥反應(yīng)中的功能機(jī)制是長(zhǎng)期來(lái)備受關(guān)注的熱點(diǎn)科學(xué)問題,。
該研究選擇擁有復(fù)雜先天免疫系統(tǒng)的魚類實(shí)驗(yàn)?zāi)Ｐ?，發(fā)現(xiàn)清道夫受體在病原誘導(dǎo)的炎癥反應(yīng)中發(fā)揮重要的負(fù)調(diào)節(jié)功能，揭示了該受體可通過競(jìng)爭(zhēng)性招募TRAF2信號(hào)蛋白以抑制TNF-a炎癥信號(hào)通路的新機(jī)制,。
表明不同的天然免疫受體及其介導(dǎo)的信號(hào)通路間存在交叉的相互調(diào)控作用,，這對(duì)全面理解炎癥信號(hào)的網(wǎng)絡(luò)調(diào)控機(jī)制與規(guī)律提供了新的科學(xué)依據(jù)。（生物谷Bioon.com）
doi: 10.4049/jimmunol.1201244
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Scavenger Receptor in Fish Is a Lipopolysaccharide Recognition Molecule Involved in Negative Regulation of NF-κB Activation by Competing with TNF Receptor-Associated Factor 2 Recruitment into the TNF-α Signaling Pathway
Zhen Meng, Xiao-Yu Zhang, Jian Guo, Li-Xin Xiang, Jian-Zhong Shao
Scavenger receptors (SRs) play crucial roles in innate immunity by acting as pattern recognition receptors. Although SRs are widely documented in mammals, data on their occurrence and functions in ancient vertebrates are limited. In this study, we report, to our knowledge, the first cloning and functional characterization of an SR molecule from teleost fish (Tetraodon nigroviridis). This SR (TnSR) was identified as a homolog to mammalian scavenger receptor class A member 5 with the conserved structure of a class A SR. TnSR contained multidomains in a type II transmembrane receptor, including an SR cysteine-rich domain, two coiled-coil collagenous domains, a transmmebrane domain, and a short N-terminal intracellular region with an unexpected TNFR-associated factor 2-binding consensus motif similar to that in human MSR molecules. Phylogenetic analysis suggested that TnSR may be an ancient member of class A SRs resulting from the close relationship between scavenger receptor class A member 5 and macrophage SR in vertebrates associated with the subtle differences in TnSR structure. Subcellular localization analysis showed that TnSR was a cell membrane receptor with homotrimer forms involved in the recognition and internalization of LPS from surface membranes into lysosomes. Functionally, TnSR expression was dramatically induced by LPS stimulation. TnSR served as a negative regulator in LPS-induced NF-κB activation by the competitive recruitment of TNFR-associated factor 2 from the TNF-α signaling pathway. To our knowledge, this is the first report showing that SR plays an inhibitory role in LPS-elicited inflammation by cross-talking with the TNF-α inflammatory pathway. These findings contribute to a better understanding of the biological and evolutionary history of the SR family.
