ハプテン誘発性アレルギー性皮膚炎における周辺CD8T細胞におけるThemisの役割

Masayuki Kitajima¹, Toshiyuki Okada¹, Kenta Nakano²

¹Department of Immunology and Pathology, Research Institute National Center for Global Health and Medicine, 1-7-1 Kounodai, Ichikawa-shi, Chiba, 272-8516 Japan.

International immunology

|September 1, 2025

まとめ

Themisタンパク質は,周辺のCD8T細胞のT細胞受容体シグナリングを調節し,アレルギー性皮膚炎に影響を与えます. 欠乏するとCD8T細胞の反応が減り,存在すると反応が強化される.

科学分野:

免疫学
T細胞生物学
アレルギー性炎症

背景:

ティムスのT細胞発育に不可欠です.
アレルギー性皮膚炎における周辺T細胞受容体 (TCR) 反応におけるその役割は不明である.

研究の目的:

周辺のT細胞,特にCD8T細胞媒介性アレルギー性皮膚炎におけるThemisの機能を調査する.
ThemisがCD8とCD4のT細胞のTCRシグナル値に影響するかどうかを判断する.

主な方法:

タモキシフェン誘導のテミス条件ノックアウト (cKO) マウスを生成した.
アレルギー性皮膚炎を誘発するためにハプテンチャレンジ (CD8のDNFB,CD4のFITC/DBP) を利用した.
評価されたT細胞浸透,サイトカイン生成 (IFNγ),転写因子発現 (T-bet,Eomes),およびin vitro TCR刺激による増殖.

主要な成果:

cKOマウスのセミス消去は,DNFB誘発の耳の腫れ,CD8T細胞の浸透,IFNγの産生,T-bet/Eomesの発現を著しく減少させた.
トランスジェニックのThemis過剰発現はDNFB誘発反応を強めた.
Themis欠乏症はFITC/ DBP誘発のCD4T細胞媒介の炎症を変化させなかった.
In vitroでは,Themis欠乏のCD8T細胞の増殖とIFNγの産生が低下したが,CD4T細胞は影響を受けなかった.
SHP-1/2の抑制により,Themis欠乏性CD8T細胞のIFNγ生成が回復した.
Grb2結合部位を欠いた変異したThemisはThemis cKO現象型を模倣した.

結論:

Themisは,アレルギー性皮膚炎の際に,周辺のCD8T細胞の反応を調節する上で重要な役割を果たします.
Themisは,Grb2結合に依存するCD8 T細胞のTCR信号の値を調節することによって機能します.
Themisは,この文脈でCD4 T細胞の反応に有意な影響を及ぼさないようです.

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