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エピテリア臓器特異的な γδ T 細胞区画を形成するためにブチロフィリンのような分子を使用する

Rafael Di Marco Barros¹, Natalie A Roberts², Robin J Dart³

¹Francis Crick Institute, London WC2A3LY, UK; Peter Gorer Department of Immunobiology, King's College London, London SE19RT, UK; MBPhD Programme, University College London, London WC1E 6BT, UK.

|September 20, 2016

まとめ

皮質細胞は,局所的なT細胞区画を形成するために特定のブチロフィリン型 (Btnl) 遺伝子を使用します. この保存されたメカニズムは,マウスとヒトの両方のT細胞受容体 (TCR) の発達に影響を与えます.

科学分野:

免疫学
発達生物学
細胞生物学

背景:

臓器特異的なガンマ・デルタ (γδ) T細胞は,組織の完全性にとって極めて重要です.
T細胞受容体 (TCR) -Vγ5 を発現するマウリンのデンドリット性表皮T細胞 (DETC) は,皮膚がん物質に対して保護します.
Skint1遺伝子はDETCのレパートリーを形作っているが,進化的な保存が欠如しているため,そのより広範な関連性は不明である.

研究の目的:

ブチロフィリン型 (Btnl) 遺伝子が他の臓器特異の γδ T 細胞区画を形成するかどうかを調査する.
このメカニズムが種間で保存されているかどうかを判断する.
地元のT細胞レパートリーを形成する際の,上皮由来Btnlの役割を明らかにする.

主な方法:

ネズミの腸内細胞におけるBtnl1発現とその γδ T細胞部位への影響について調査した.
T細胞受容体 (TCR) 依存反応を誘発するBtnl1とBtnl6の共同機能を分析した.
選択的なT細胞反応におけるBTNL3とBTNL8を発現するヒトの大腸上皮細胞を検査した.

主要な成果:

ネズミの腸細胞で発現するBtnl1は,微生物または食品抗原とは独立して,局所的なTCR-Vγ7(+) γδT細胞区画を形成する.
Btnl1とBtnl6は,特異的に腸のVγ7(+) 細胞でTCR依存反応を誘発するために協力する.
人間の腸内皮質細胞はBTNL3とBTNL8を発現し,それらは共同でヒトの大腸Vγ4 ((+) 細胞の選択的TCR依存反応を誘発する.

結論:

エピテリアが臓器特異のBTNL/Btnl遺伝子を利用して局所的なT細胞区画を形成する保存されたメカニズムが存在する.
この上皮による選択はT細胞受容体 (TCR) のレパートリーを形成する.
この発見は皮膚を超えて腸まで広がり免疫系の組織化における基本的な原理を明らかにしています

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