Tヘルパー1の免疫には,CD4+T細胞における補完体主導のNLRP3炎症体活性が必要である

Giuseppina Arbore¹, Erin E West², Rosanne Spolski²

¹MRC Centre for Transplantation, Division of Transplant Immunology and Mucosal Biology, King's College London, London SE1 9RT, UK.

Science (New York, N.Y.)

|June 18, 2016

まとめ

NLRP3炎症体はヒトT細胞で活性化し,Tヘルパー1の反応を誘発する. この発見は炎症体の機能に関する理解を生まれつきの免疫を超えて広げています

科学分野:

免疫学
細胞生物学

背景:

NLRP3炎症体は,抗原を呈現する細胞におけるインタールキン-1βの成熟を調節することが知られている.
ヒトの適応性免疫細胞,特にT細胞におけるその役割は,ほとんど説明されていない.

研究の目的:

人間のCD4 ((+)) T細胞におけるNLRP3炎症体の構成と機能を調査する.
適応性T ((H)) 1免疫反応におけるNLRP3炎症体の活性への影響を決定する.

主な方法:

人間のCD4 ((+)) T細胞におけるNLRP3炎症体組成の分析.
カスパース-1依存型インタールイキン-1β分泌の評価
インターフェロンγの産生とTヘルパー1の分化に関する評価
C5活性化,C5aR1およびC5aR2の調節に関する調査.
自己炎症疾患とマウスモデルにおけるNLRP3の活性に関する試験.

主要な成果:

NLRP3炎症ゾームは,ヒトのCD4 ((+)) T細胞で組み合わされる.
アセンブリはカスパース-1依存型インタールイキン-1βの分泌を誘発し,インターフェロン-γの産生とTヘルパー1の分化を促進する.
NLRP3の組み立ては細胞内C5の活性化とC5aR1の刺激に依存し,C5aR2は負の調節剤として作用する.
T細胞における異常なNLRP3活動は,炎症状態と関連しています.

結論:

NLRP3炎症体の活動は,正常な適応性Tヘルパー1応答に不可欠です.
NLRP3炎症体は先天的な免疫細胞に限定されず,適応免疫において役割を果たします.
T細胞におけるNLRP3の機能を理解することで,自己炎症性疾患と感染モデルへの洞察が得られます.

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