STINGは,感覚ニューロンのタイプIインターフェロンシグナル伝達により,知覚を制御する

Christopher R Donnelly¹, Changyu Jiang², Amanda S Andriessen²

¹Center for Translational Pain Medicine, Department of Anesthesiology, Duke University Medical Center, Durham, NC, USA. christopher.donnelly@duke.edu.

Nature

|January 14, 2021

まとめ

STING-IFN-I経路は痛みの知覚を制御しています神経細胞の興奮性を抑制することで,慢性疼痛の治療に新しい標的を提供します.

科学分野:

免疫学
神経科学
痛みに関する研究

背景:

STING (インターフェロン遺伝子の刺激剤) はDNAの重要な先天的な免疫センサーです.
STINGの活性化は,病原体と癌細胞のクリアランスを決定するタイプIインターフェロン (IFN- I) とサイトカインを誘発する.
痛みの信号は nociceptorsによって伝達され有害な刺激に警鐘を鳴らして宿主の防御を助けます

研究の目的:

痛みの感受におけるSTINGの役割を調査する.
周辺感覚ニューロンのSTING-IFN-I信号軸を調査する
疼痛管理のための潜在的な治療目標としてSTINGを特定する.

主な方法:

STING欠乏したマウスを用いて,悪感反応を評価した.
IFN-Iシグナルがノシセプターに与える影響を研究した.
ネズミとヒト以外の霊長類に注射されたSTING活性化剤.

主要な成果:

STINGまたはIFN-I信号が欠けていたマウスは,痛みに対する感受性が高まった.
腸内STINGの活性化により,複数の種で痛みの緩和が顕著であった.
IFN- Iは,マウス,サル,ヒトの神経受容体の興奮を迅速に抑制しました.

結論:

STING-IFN-Iシグナル伝達経路は生理的な痛み感知の重要なレギュラーです
STINGの活性化により,強力な抗発覚効果が示されています.
この経路は慢性的な痛みに対する新しい治療目標です

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