健康と炎症性腸疾患における結腸上皮細胞の多様性
Kaushal Parikh1,2, Agne Antanaviciute1,2,3, David Fawkner-Corbett1,2,4
1Medical Research Council (MRC) Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine (WIMM), John Radcliffe Hospital, University of Oxford, Oxford, UK.
Nature
|March 1, 2019
まとめ
研究者は新しい結腸上皮細胞亜型と pH感知細胞を特定しました 炎症性腸疾患 (IBD) では,コップレット細胞の変化と減少したWFDC2抗プロテアスがバリア崩壊に寄与する.
科学分野:
- 胃腸内科
- 細胞生物学
- 免疫学
背景:
- 大腸の表皮は宿主と微生物の相互作用,粘膜免疫,栄養素のリサイクル,バリア機能に不可欠です.
- 表皮壁の崩壊は炎症性腸疾患 (IBD) の特徴ですが,特定の細胞サブタイプの貢献は不明です.
研究 の 目的:
- IBD患者と対照群の単一の結腸上皮細胞のプロファイルを作成し,バリアの整合性における細胞亜型の役割を理解する.
- IBDにおける上皮壁機能不全の原因となる新しい細胞サブタイプと分子メカニズムを特定する.
主な方法:
- IBD患者と健康な対照群の結腸上皮細胞の単細胞RNA配列解析
- 異なる表皮細胞サブタイプと転写状態の識別と特徴付け
- 特定された分子と細胞過程の in vivo 検証
主要な成果:
- クリプト内の先駆体,コロノサイト,ゴブレット細胞のグラデントを含む,これまで知られていなかった結腸上皮細胞サブタイプの発見.
- 炎症と癌で調節不能な新しいpH感知吸収細胞 (OTOP2とウロガニリンを発現する) の特定
- IBDでは,WFDC2のダウンレギュレーションと一致する,バクテリアの成長を阻害し,上皮壁の完全性を保持する抗タンパク質の位置的改造が観察されました.
結論:
- 単細胞プロファイリングは,複雑な結腸上皮細胞の異質性を明らかにし,新しい細胞タイプを特定します.
- WFDC2は,細菌の侵入を阻害し,粘膜の炎症を軽減することによって,上皮壁の機能を維持する上で重要な役割を果たします.
- 特定の上皮細胞サブタイプとWFDC2のような分子の不調は,IBDにおけるバリア崩壊の根本的な決定因子です.
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