血清のアミロイドAタンパク質は,病原性Th17細胞を誘発し,炎症性疾患を促進する
June-Yong Lee1, Jason A Hall1, Lina Kroehling1
1The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA.
Cell
|December 24, 2019
まとめ
血清アミロイドタンパク質 (SAA) はTヘルパー17 (Th17) 細胞を調節する. SAAは病原性炎症とTh17媒介の自己免疫疾患を促進し,SAAを治療標的として示唆しています.
科学分野:
- 免疫学
- 分子生物学
- 自己免疫 疾患
背景:
- Tヘルパー17 (Th17) 細胞は,宿主防御に不可欠なインタールイキン17 (IL-17) サイトカインを産生しますが,自己免疫疾患にも関与しています.
- 腸内では,Th17細胞の分化と機能は,血清アミロイドタンパク質 (SAA) を含む微生物群と局所環境のシグナルによって影響を受けます.
研究 の 目的:
- 血清アミロイドタンパク質 (SAA) がTh17細胞の分化と機能を制御する役割を調査する.
- SAAがTh17媒介の炎症および自己免疫状態の発達にどのように貢献するか解明する.
主な方法:
- SAA1,SAA2およびSAA3のインビボ機能を研究するために,機能喪失および機能獲得マウスモデルを使用した.
- SAAがSTAT3シグナル伝達を含むTh17細胞の分化と炎症反応を調節する分子メカニズムを調査した.
主要な成果:
- SAAはSTAT3活性化サイトカインと併用して,病原性炎症を誘発するTh17細胞の分化プログラムを実行することを実証した.
- SAA1,SAA2,SAA3は,局所的および全身的な効果を持つTh17媒介の炎症性疾患の促進において,異なる役割を果たしていることが示された.
- SAAによって調節された特定のT細胞信号伝達経路を特定した.
結論:
- 血清のアミロイドタンパク質は,Th17細胞生物学において二重の役割を果たし,ホメオスタティック機能と病原性機能の両方を調節する.
- SAA調節されたT細胞シグナル伝達経路は,自己免疫疾患の新たな抗炎症療法を開発するための有望なターゲットです.
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