炎症記憶は皮膚上皮幹細胞を組織損傷に敏感にする

Shruti Naik¹, Samantha B Larsen¹, Nicholas C Gomez¹

¹Robin Chemers Neustein Laboratory of Mammalian Cell Biology and Development, Howard Hughes Medical Institute, The Rockefeller University, New York, New York 10065, USA.

Nature

|October 19, 2017

まとめ

皮膚の幹細胞は炎症の記憶を形成し損傷後の障害物の修復を加速しますこの適応はAim2炎症体の活性化によって引き起こされ,反応力を高めますが,がんのリスクも高まります.

科学分野:

免疫学
幹細胞生物学
皮膚科

背景:

防御に不可欠な皮膚の障壁は皮質幹細胞 (EpSCs) によって維持されます
EpSCの炎症への反応とその長期的な影響は完全に理解されていません.
EpSCは炎症性損傷に脆弱です

研究の目的:

マウスの上皮幹細胞 (EpSCs) への急性炎症の持続的な影響を調査する.
EpSC が炎症イベントに適応し"記憶"するメカニズムを特定する.
この幹細胞の記憶が皮膚の障壁の修復にどう影響するか理解するためです

主な方法:

マウスの急性炎症モデルです
炎症後のEPSC機能と遺伝子発現の分析
Aim2,caspase-1,interleukin-1βを含む遺伝子操作でした

主要な成果:

マウスのEPSCは急性炎症の記憶を長持ちさせ,二次損傷後のバリアの回復を加速します.
EpSCにおけるこの機能的適応は,皮膚に存在するマクロファージとT細胞とは無関係です.
EpSCは,ストレス反応遺伝子の染色体アクセシビリティを維持し,Aim2炎症体シグナル伝達により,炎症に再暴露されたときに迅速な転写を可能にします.
Aim2,caspase-1,またはinterleukin-1βの喪失は,EPSCにおけるこの炎症記憶を消去する.

結論:

炎症の内在的な記憶を持ち組織修復を促します
このEPSCの炎症記憶を確立し維持するために,Aim2炎症体の経路は極めて重要です.
炎症によるEpSCの感受性の上昇は,自己免疫疾患や癌への感受性を高めることがあります.

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