皮質細胞由来のアトピー性皮膚炎のサイトカインであるTSLPは,神経細胞を活性化し,を誘発する
Sarah R Wilson1, Lydia Thé, Lyn M Batia
1Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
Cell
|October 8, 2013
まとめ
研究者らは,上皮細胞は,感受性ニューロンを直接活性化するために,チムスストロマルリンパポエチン (TSLP) を放出し,アトピー性皮膚炎 (AD) でを起こすことを発見しました. このTSLPの放出は,皮膚細胞内のORAI1/NFATカルシウム経路によって調節されます.
科学分野:
- 免疫学 免疫学とは
- 神経科学は神経科学である.
- 皮膚科 皮膚科について
背景:
- アトピー性皮膚炎 (AD) は慢性炎症性皮膚疾患で,人口の10%に及ぶ.
- 深刻なADは,喘息とアレルギー性鼻炎につながる可能性があり,その進行は"アトピー行進"と呼ばれています.
- 胸筋筋リンパポエチン (TSLP) 信号伝達は,ADの病原性およびアトピー的な進行に関与しています.
研究 の 目的:
- アトピー性皮膚炎におけるを媒介する上皮細胞由来TSLPの役割を調査する.
- 皮膚上皮細胞からTSLPの放出を調節する分子機構を特定する.
- の行動を促進するTSLPのニューロンの標的を明らかにする.
主な方法:
- ケラチノサイトからのTSLP放出を調査した.
- ケラチノ細胞におけるORAI1/NFAT経路を研究するために,カルシウム画像を用いた.
- TSLPが感覚ニューロン,特にTRPA1陽性ニューロンに及ぼす影響を調べました.
- TSLP刺激に反応するの行動を評価した.
主要な成果:
- 皮質細胞は,TSLP経由で皮膚の感覚神経細胞と通信し,を誘発する.
- ORAI1/NFATカルシウムシグナル伝達経路は,ケラチノ細胞からのTSLP放出に不可欠です.
- TSLPは,TRPA1陽性感受性ニューロンのサブセットを直接活性化させ,を誘発する.
- この経路は,皮膚と呼吸道の両方の炎症反応に寄与する.
結論:
- TSLP経由で表皮-ニューロン通信を含むアトピー性皮膚炎におけるのシグナル伝達の新しいメカニズムが特定されました.
- ORAI1/NFAT経路は,TSLPの放出を調節し,カルシウムシグナリングとを結びつける.
- TSLPまたはそのシグナル伝達経路をターゲットにすることで,アトピー性皮膚炎とアトピー性マーチに対する治療戦略を提供することができます.
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