感染したアポプトシス細胞の先天的な免疫認識は,T(H) 17細胞の分化を指示する
Miriam Beer Torchinsky1, Johan Garaude, Andrea P Martin
1Immunology Institute, Department of Medicine, Mount Sinai School of Medicine, 1425 Madison Avenue, New York, New York 10029, USA.
Nature
|March 6, 2009
まとめ
生まれながらの免疫細胞は,感染したアポプトシス細胞を認識し,Tヘルパー17 (T(H) (17) 細胞の分化を引き起こします. このプロセスは宿主の防御に不可欠ですが,自己免疫疾患にもつながる可能性があります.
科学分野:
- 免疫学 免疫学とは
- 細胞生物学 細胞生物学
- 微生物学 微生物学とは
背景:
- 適応性免疫には,CD4 Tヘルパー細胞が,Tヘルパー1 (T(H) 1 ,Tヘルパー2 (T(H) 2 ,および最近特定されたTヘルパー17 (T(H) 17) 細胞のようなサブセットに微分化します.
- T (H) 17細胞は,宿主の病原体に対する防御に不可欠です.
- 実験室内での研究では,変形成長因子β (TGF-β) とインタールイキン-6 (IL-6) がT(H) 17の分化を引き起こし,IL-23がそれらの拡大を促進することを示しているが,実験室内でのトリガーは不明である.
研究 の 目的:
- T(H) 17細胞の微分化に必要なサイトカインの組み合わせを誘導する in vivo 条件を解明する.
- 感染したアポプトシス細胞がT(H) 17の免疫反応を誘発する役割を調査する.
- T(H) 17細胞,自己免疫,および病原体誘発のアポトーシスとの関係を調査する.
主な方法:
- マウスとヒトのシステムにおける,デンドリット細胞と感染したアポプトティック細胞の相互作用を研究した.
- ネズミのCitrobacter rodentium感染モデルを使用して,腸内表皮におけるT(H) 17反応を研究しました.
- 分析されたサイトカインの産生とT細胞の微生物信号と無微生物信号によるアポプトティック細胞のファゴサイトーシス後のT細胞の分化.
主要な成果:
- デンドリット細胞による感染したアポプトシス細胞のファゴシトーシスは,同効果のTGF-βとIL-6の産生を特異的に誘発する.
- 病原体に関連した分子パターンの認識と,アポプトシス細胞におけるホスファティジルセリンは,このサイトカイン誘導を媒介する.
- 感染中にアポトーシスを阻害すると,T(H) 17の分化が低下し,感染していないアポトーシス細胞のファゴサイトーシスは,T細胞の分化を促進した.
結論:
- 感染したアポプトシス細胞は,T(H) 17細胞の分化を指示する重要な先天性免疫信号である.
- アポトーシスを誘発する病原体は,好ましくは,T (H) 17媒介免疫を誘発する可能性があります.
- 感染したアポプトシス細胞の認識を理解することで,自己免疫疾患のメカニズムに光を当てることができます.
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