Ro60自己抗原は内在的なレトロエレメントと結合し,炎症性遺伝子発現を調節する

T Hung¹, G A Pratt², B Sundararaman²

¹Genentech, South San Francisco, CA 94080, USA. behrens.tim@gene.com hungt2@gene.com geneyeo@ucsd.edu.

Science (New York, N.Y.)

|September 19, 2015

まとめ

ロ60を標的にするオートアンチボディはAluレトロエレメントと関連しています. これらの元素は,Ro60に結合すると,炎症を促進し,全身性狼の病原性における役割を示唆する.

科学分野:

分子生物学
免疫学
遺伝学

背景:

Ro60に対する自己抗体は,全身性狼症 (SLE) とシェーグレン症候群において一般的です.
Ro60とその関連RNAの病原性における役割は不明である.

研究の目的:

Ro60とその結合RNAとの関連を調査する.
SLEにおけるI型インターフェロンシグナル伝達と炎症に対するRo60関連RNAの寄与を決定する.

主な方法:

Ro60関連RNAをヒトの細胞系に分類する
アルウレトロエレメントのトランスクリプト発現とタイプIインターフェロンによる誘導を分析する.
アルーRNAとインターフェロン調節遺伝子発現に対する Ro60 削除の影響を評価する.
抗Ro60陽性SLE免疫複合体と全血サンプルにおけるAlu RNAの検出

主要な成果:

Ro60は内生アルウレントから派生したRNAモチーフに結合する.
AluトランスクリプトはI型インターフェロンによって誘発され,炎症誘発性サイトカインの分泌を刺激する.
Ro60の消去は,Alu RNAとインターフェロン調節遺伝子発現の増加につながります.
ALURNAはSLEの免疫複合体に存在し,SLEの血液サンプルでは上位調節されます.

結論:

ループス自己抗原 Ro60,アルウレトロエレメント,およびタイプIインターフェロンとの間のリンクを確立します.
アルウ・レトロエレメントと Ro60との相互作用が SLEの病原化に寄与することを示唆している.

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