JP6385732B2 - 免疫応答制御剤 - Google Patents
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Description
(3)樹状細胞の抗原応答機能がサイトカイン産生機能である、(2)に記載の免疫応答制御剤。
(4)(1)〜(3)のいずれかに記載の免疫応答制御剤を含有する医薬。
1)IL−6又はIL−17刺激したDCのmRNAの調製
三人の健常ヒト血液より回収したヒト末梢血単核細胞(2×106個)を1mLのAIM−V(登録商標)(Life Technologies)に懸濁して1時間インキュベートし、細胞を底面に接着させた。接着した細胞を0.05mg/mLのIL−4及びGM−CSFの存在下で7日間培養することで、ヒト単球由来樹状細胞(Monocyte−derived Dendritic Cell、MoDC)とした。
1)のIL−6刺激又はIL−17刺激を受けたMoDC及びコントロールのMoDCから回収したmRNA画分に対して、東レ株式会社に委託してマイクロアレイ解析を行った。
1)LPS又はポリI:C刺激したDCのmRNAの調製
実験例1の1)と同様にして調製した培養7日目のMoDCに、LPS(0.5μg/mL)又はポリI:C(10μg/mL)を培地に添加してさらに8時間培養を続けた。その後、実験例1の1)と同じ処理を行って、LPS刺激又はポリI:C刺激を受けたMoDC、及びコントロールのMoDCからそれぞれmRNAを回収した。
1)のLPS刺激又はポリI:C刺激を受けたMoDC及びコントロールのMoDCから回収したmRNA画分に対して、目的のmiRを検出する合成プライマーを用いて定量PCR解析を行った。
表3(IL−6刺激で発現量が上昇するmiR)のhsa−miR−3646及びこれに対する阻害性核酸(hsa−miR−3646−I)を、SIGMA−ALDRICH(http://www.sigmaaldrich.com/life−science/functional−genomics−and−rnai/mirna/microrna−mimics.htmlに依頼してそれぞれ化学合成した。
実施例1のhsa−miR−3646及びhsa−miR−3646−Iを、IL−17刺激によって発現量が減少するhsa−miR3934−5p及びこれに対する阻害性核酸であるhsa−miR−3934−5p−I(いずれもSIGMA−ALDRICHに合成を依頼)に換えて、実施例1と同様の実験を行った。その結果を、図23〜図26に示す。
<実施例3>
実施例1のhsa−miR−3646及びhsa−miR−3646−Iを、LPS刺激によって発現量が上昇するhsa−miR−1266−5p(SIGMA−ALDRICHに合成を依頼)に換え、DCへの刺激をLPSのみとした以外は実施例1と同様の実験を行い、IFN−βの発現量の変化を測定した。その結果を、図27に示す。
表5(LPS刺激で発現量が上昇するmiR)のhsa−miR−224−5p及びこれに対する阻害性核酸(hsa−miR−224−5p−I)をそれぞれ化学合成した(いずれもSIGMA−ALDRICHに合成を依頼)。
実施例4のhsa−miR−224−5pを、LPS刺激又はポリI:C刺激によって発現量が上昇するhsa−miR−224−3p又はhsa−miR−20b−5p(いずれもSIGMA−ALDRICHに合成を依頼)に換えて、実施例4と同様の実験を行った。その結果を、図30〜図31に示す。
Claims (4)
- 表1に示されるマイクロRNA、前記マイクロRNAと相補的なマイクロRNA、前記マイクロRNA及び前記相補的なマイクロRNAに対する阻害性核酸並びにそれらの機能的等価物よりなる群から選択される少なくとも一種以上の核酸を有効成分とする、樹状細胞の抗原応答機能を制御するための免疫応答制御剤であって、前記機能的等価物は、表1に示されるマイクロRNAをコードする核酸、表1に示されるマイクロRNAの塩基配列の一部が修飾されたヌクレアーゼ分解に対して安定な核酸若しくはこれらのキメラRNA、又は表1に示されるマイクロRNAに対する阻害性核酸をコードする核酸、表1に示されるマイクロRNAに対する阻害性核酸の塩基配列の一部が修飾されたヌクレアーゼ分解に対して安定な核酸若しくはこれらのキメラRNAであって、かつ樹状細胞の抗原応答機能を制御することができる核酸又はキメラRNAである、前記免疫応答制御剤。
- 樹状細胞の抗原応答機能が樹状細胞の抗原提示機能又はサイトカイン産生機能である、請求項1に記載の免疫応答制御剤。
- さらに樹状細胞の抗原応答機能の制御を介してT細胞のサイトカイン産生機能を制御するための、請求項1又は2に記載の免疫応答制御剤。
- 請求項1〜3のいずれか一項に記載の免疫応答制御剤を含有する医薬。
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