慢性炎症は,セリアック病における組織内定の免疫を永久に変形させます

Toufic Mayassi¹, Kristin Ladell², Herman Gudjonson³

¹Committee on Immunology, University of Chicago, Chicago, IL, USA; Department of Medicine, University of Chicago, Chicago, IL, USA.

Cell

|February 12, 2019

まとめ

セリアック病 (CeD) のグルテンによる慢性炎症は,特定の免疫細胞 (Vγ4+/Vδ1+ IELs) を枯渇させる. グルテン除去後でさえ腸の免疫の再構成は永久的です

科学分野:

免疫学
胃腸内科
細胞生物学

背景:

組織に宿るリンパ球は免疫監視に不可欠です.
慢性炎症に対するこれらの細胞の反応は十分に理解されていません.
セリアック疾患 (CeD) は,抗原駆動性炎症を研究するためのモデルを提供します.

研究の目的:

結腸病において,グルテン誘発の慢性炎症が組織内定のT細胞受容体ガンマデルタ (TCRγδ+) 内皮内リンパ球 (IELs) に与える影響を調査する.
炎症と回復の間にIEL集団の変化の基礎となる分子機構を理解する.

主な方法:

乳がん患者におけるVγ4+/ Vδ1+ IELおよびそのT細胞受容体 (TCR) の分析
腸内におけるブチロフィリン類 (BTNL) 分子の発現 (BTNL3/BTNL8) の評価
食事からグルテンを除外した後のIEL集団とBTL8発現のモニタリング

主要な成果:

CeDにおけるグルテンの曝露は,BTNL3/BTNL8を認識するVγ4+/Vδ1+IELを大幅に減少させた.
BTNL8の発現が低下した新しいニッチが,独特のTCRを持つグルテン感受性Vδ1+IELの拡大とともに出現した.
グルテン除去はBTNL8発現を回復させたが,Vγ4+/ Vδ1+ IELサブセットを完全に再構成しなかった.

結論:

CeDにおける慢性的なグルテン炎症は,組織に居住するTCRγδ+ IEL区間を永久に変化させます.
この研究は腸内疾患における腸内免疫の持続的な再構成を明らかにしています
これらの発見は慢性的な炎症が免疫細胞集団に及ぼす長期的な影響を強調しています

キーワード:

ブチロフィリンのような分子セリアック病イントラエピテリアリンパ球組織に居住するリンパ球 γδ T細胞

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