2012年11月26日 訊 /生物谷BIOON/ --一項(xiàng)新研究發(fā)現(xiàn)基因Arih2是免疫系統(tǒng)功能的基礎(chǔ),，能對(duì)免疫反應(yīng)是否的開啟起決定性作用,。它的發(fā)現(xiàn)能對(duì)治療慢性感染如HIV，免疫系統(tǒng)疾病以及慢性炎癥疾病如類風(fēng)濕關(guān)節(jié)炎和敗血癥的治療帶來新思路,。
研究結(jié)果發(fā)表在Nature Immunology雜志上,。Arih2被發(fā)現(xiàn)存在于免疫系統(tǒng)哨兵樹突狀細(xì)胞中，其在抵抗外來入侵者發(fā)揮了至關(guān)重要的作用,。
Arih2是免疫反應(yīng)是否應(yīng)啟動(dòng)或關(guān)閉最根本,，最重要的決定因子。如果作出錯(cuò)誤的決定,，機(jī)體將屈服于感染,，或發(fā)生自身免疫性疾病,。我們的免疫系統(tǒng)運(yùn)作良好，對(duì)許多感染已經(jīng)建立了精確生物機(jī)制以逃避或?qū)垢腥尽?/p>
但在進(jìn)化過程中,，一些生物已經(jīng)進(jìn)化耗盡我們的免疫系統(tǒng),，這也是我們罹患HIV，乙肝和結(jié)核病的原因,。Ebert博士說,，研究小組正在分析短的時(shí)間內(nèi)關(guān)閉Arih2對(duì)慢性感染免疫反應(yīng)的影響。Arih2具有獨(dú)特的結(jié)構(gòu),，我們認(rèn)為這是一個(gè)很好的藥物靶標(biāo),，但開發(fā)出以此為靶點(diǎn)的藥物還需數(shù)年的研究。（生物谷：Bioon.com）
doi:10.1038/ni.2478
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PMID:
ARIH2 is essential for embryogenesis, and its hematopoietic deficiency causes lethal activation of the immune system
Amy E Lin,Gregor Ebert,Yongkai Ow,et al.
The E3 ligase ARIH2 has an unusual structure and mechanism of elongating ubiquitin chains. To understand its physiological role, we generated gene-targeted mice deficient in ARIH2. ARIH2 deficiency resulted in the embryonic death of C57BL/6 mice. On a mixed genetic background, the lethality was attenuated, with some mice surviving beyond weaning and then succumbing to an aggressive multiorgan inflammatory response. We found that in dendritic cells (DCs), ARIH2 caused degradation of the inhibitor IκBβ in the nucleus, which abrogated its ability to sequester, protect and transcriptionally coactivate the transcription factor subunit p65 in the nucleus. Loss of ARIH2 caused dysregulated activation of the transcription factor NF-κB in DCs, which led to lethal activation of the immune system in ARIH2-sufficent mice reconstituted with ARIH2-deficient hematopoietic stem cells. Our data have therapeutic implications for targeting ARIH2 function.
