タンパク質結晶は2型免疫を促進し,抗体治療によって逆転する
Emma K Persson1,2, Kenneth Verstraete3,4, Ines Heyndrickx1,2
1Immunoregulation Unit, VIB Center for Inflammation Research, Ghent, Belgium.
Science (New York, N.Y.)
|May 25, 2019
まとめ
ガレクチン10 (Gal10) タンパク質でできたシャーコット・レイデン結晶 (CLC) は,喘息で発見される. これらのタンパク質結晶は 喘息の症状を助長し,特定の抗体によって溶解され,新たな治療標的となる.
科学分野:
- 免疫学
- タンパク質結晶学
- 呼吸器医学
背景:
- ガレクチン10 (Gal10) で構成されるシャーコット・レイデン結晶 (CLC) は,喘息のようなエオシノフィル性疾患で頻繁に観察される.
- タンパク質の自発的な結晶化は in vivoではまれですが,CLCは特定の疾患の状況で一般的です.
研究 の 目的:
- 喘息の病原性におけるガレクチン10 (Gal10) タンパク質結晶の役割を調査する.
- 喘息の治療戦略としてCLCを標的とする可能性を調査する.
主な方法:
- in vitroで成長したGal10結晶を持つ患者のCLC構造の比較
- 結晶のGal10と溶解性のGal10ミューテインをマウスの喘息モデルに投与する.
- 喘息の特徴の逆転を評価するために,CLC結晶化インターフェースを標的とする抗体による治療.
主要な成果:
- 患者のCLCは,インビトロの結晶と同一の結晶包装とGal10構造を示します.
- 結晶のGal10は2型補助体として作用し,先天性および適応性免疫を刺激しますが,溶解性Gal10は惰性です.
- CLC結晶化インターフェースを標的とした抗体は,CLCを溶解させ,炎症,IgE合成,および小鼠モデルにおける気管の過剰反応を逆転させた.
結論:
- タンパク質結晶,特にCLCは 喘息の主要な特徴を駆動する可能性があります.
- 結晶溶解抗体でCLCを標的にすることは,喘息治療の新たな治療法です.
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