健康な脳老化と認知障害における脳脊髄液の免疫不調

Natalie Piehl¹, Lynn van Olst¹, Abhirami Ramakrishnan¹

¹The Ken & Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

Cell

|December 14, 2022

まとめ

脳脊髄液の免疫は年齢や認知障害によって変化します老化により単細胞の脂質輸送遺伝子が増加し免疫細胞のシグナル伝達と脳への侵入メカニズムが変化します

科学分野:

神経免疫学
老化に関する研究
神経変性疾患

背景:

脳脊髄液 (CSF) は調節された免疫系を宿している.
老化や神経変性疾患によってCSFの免疫がどのように変化するかについてはほとんど知られていません.

研究の目的:

健康な脳の老化過程における CSF 免疫細胞のプロフィールの変化を調査する.
認知的に正常な人と障害のある人の間でのCSF免疫を比較する.

主な方法:

CSFのサンプルで単細胞RNAの配列を決定した.
分析対象は,認知的に正常な被験者45名 (年齢54~82歳) と認知障害のある被験者14名でした.

主要な成果:

単細胞は年齢とともに脂質輸送遺伝子発現が増加した.
認知障害の被験者は,単細胞における脂質輸送遺伝子発現の低下を示した.
CD8 T細胞への変異したサイトカインシグナル伝達と,CD8 Tエフェクタルの記憶細胞におけるC- X- Cモチーフ・ケモカイン受容体6 (CXCR6) のアップレギュレーションが観察されました.
脊髄液中のC-X-Cモチーフキモカインリガンド16 (CXCL16) の上昇は,T細胞の脳への侵入に作用することを示唆している.

結論:

脳の健康的な老化は脊髄液の免疫不調と関連しています
認知障害は,単細胞脂質輸送とT細胞ケモカイン受容体発現の変化を含む,明確なCSF免疫変化を含む.
CXCL16-CXCR6信号は,抗原特異性T細胞の脳内浸透を促進する可能性があります.

キーワード:

アルツハイマー病 T細胞適応免疫老化する脳脊髄液認知障害

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