多発性硬化症の進行を促すのは骨髄の血液形成
Kaibin Shi1, Handong Li2, Ting Chang3
1Department of Neurology, Institute of Neuroimmunology, Tianjin Medical University General Hospital, Tianjin 300052, China; Center for Neurological Diseases, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.
Cell
|June 16, 2022
まとめ
多発性硬化症では 骨髄の幹細胞が 骨髄形成にシフトし 中枢神経系 (CNS) に侵入する 炎症細胞を増やす. 骨髄をターゲットにすることで MSの新たな治療法が見つかるかもしれません
科学分野:
- 免疫学
- 神経科学
- 血液学
背景:
- 多発性硬化症 (MS) は,中枢神経系 (CNS) に影響するT細胞媒介の自己免疫疾患である.
- MSの病原性における骨髄造血幹細胞 (HSPCs) の役割は十分に理解されていません.
- HSPCは免疫活性化に反応することが知られている.
研究 の 目的:
- MSにおける自己反応性T細胞と骨髄HSPCの相互作用を調査する.
- 多発性硬化症患者の骨髄における 変異性骨髄形成を促すメカニズムを探る
- 骨髄のニッチをターゲットにすることで,多発性硬化症における中枢神経系の炎症に影響を及ぼすかどうかを判断する.
主な方法:
- MS患者におけるHSPC系統の歪みとT細胞拡張の分析
- MSのマウスモデルである実験的な自己免疫脳髄炎 (EAE) の系統追跡.
- 骨髄における細胞移動経路 (CXCR4) とシグナル伝達軸 (CCL5-CCR5) の調査
主要な成果:
- MS患者における骨髄HSPCは,クローンT細胞の拡大による骨髄系バイアスを示しています.
- EAEマウスは中枢神経系に浸透する中性子とLy6Chigh単細胞を産生する骨髄骨髄形成が増加した.
- ミエリン反応性T細胞はCXCR4経由で骨髄に移動し,CCL5-CCR5軸は骨髄形成を促し,中枢神経の炎症と脱ミエリン化を悪化させる.
結論:
- T細胞の相互作用によって引き起こされる異常骨髄形成は,MSにおける中枢神経系の病変に寄与する.
- 骨髄のニッチはMSの病原化に 重要な役割を果たします
- 骨髄の微小環境をターゲットにすることで MSやその他の自己免疫疾患の 治療戦略が実現できます
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