T細胞のLKB1欠乏は,胃腸ポリポシスの発症を促進する

M C Poffenberger^1,2, A Metcalfe-Roach¹, E Aguilar^1,2

¹Goodman Cancer Research Centre, McGill University, Montreal, Quebec H3A 1A3, Canada.

Science (New York, N.Y.)

|July 28, 2018

まとめ

T細胞のSTK11腫瘍抑制剤の喪失は胃腸多重症を引き起こす. IL-6とSTAT3シグナリングを含む炎症をターゲットにすることで,ピュッツ・ジェガー症候群のモデルでポリプの成長が低下しました.

科学分野:

腫瘍学
免疫学
胃腸内科

背景:

STK11 (肝臓キナーゼB1,LKB1をコードする) の生殖系統変異は,がんへの予備性障害であるピュッツ・ジェーサー症候群 (PJS) を引き起こします.
PJSは胃腸 (GI) のポリプ形成によって特徴づけられ,がんのリスクが増加します.

研究の目的:

T細胞特異的なSTK11喪失が GIポリポシスを促進する役割を調査する.
PJSのポリップ発症を誘発する炎症メカニズムを特定する

主な方法:

Stk11欠乏性T細胞マウス (LThet) の生成
炎症マーカーに関するLThetマウス,Stk11+/-マウス,およびヒトPJS患者のポリプの分析
ポリプの成長に対するT細胞,IL-6,またはSTAT3信号の治療標的の評価.

主要な成果:

ネズミのT細胞におけるStk11の異質欠失は,GIポリポシスを誘発した.
ポリプは慢性炎症で,免疫細胞の浸透,STAT3の活性化,およびIL-6,IL-11,CXCL2の上昇が特徴でした.
Stk11欠乏した動物における抑制されたポリプの増殖を信号するT細胞,IL-6,またはSTAT3の抑制.

結論:

LKB1媒介の炎症は,PJSにおける腸多重症の組織外的調節剤として作用する.
炎症経路をターゲットにすることで,PJSおよび関連疾患に対する潜在的な治療戦略を提示します.

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