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2015年6月 3日 (水)

リンパ系組織が脳まで達していたという350年の常識を塗り替える新事実が判明

Lymphatic_system

Researchers Find Missing Link Between the Brain and Immune Systemという記事の紹介です。

この記事で紹介されているバージニア医学大学のチームの論文ではなんと新たに大脳皮質に到達するリンパ系組織を発見したということで、教科書が書き換わるとんでもない大発見になります。

今までの常識と矛盾点

リンパ系組織とはリンパ球や白血球などが含まれるリンパ液を作って体中に運ぶ開放循環系です。はじめに記載されたのはルドベックとバートリンが別々に出版した論文で1653年までさかのぼります。それ以来、体中にリンパ系組織が張り巡らされていることが知られていますが、脳だけは別で、どうやら免疫細胞は脳まで到達しない・できないというのが常識でした。

しかし、この常識では説明しづらい病気に中枢神経原発悪性悪性リンパ腫というのがあります。悪性リンパ腫の初発時に、脳や脊髄および眼にだけある状態です。

脳にはリンパ系組織がありません。それなのになぜ悪性リンパ腫が発生するのかまだ分かっていません。炎症などで浸潤してきたリンパ球が腫瘍化するとか、他で発生したリンパ腫が免疫学的に保護されている脳内にだけ残ったとかの説がありますが、未だ解決されていません。

上記の引用のように脳は脳血管関門で守られているのでリンパ系組織がないというのは常識で、グリア細胞などが免疫細胞の代わりの役割をはたすのだと考えられていました。

新発見

バージニア医学大学のJonathan Kipnis教授のチームは髄膜と呼ばれる脳を覆っている膜を観察していました。第一著者のアントニー(Antoine Louveau)さんによると

“There was one trick: We fixed the meninges within the skullcap, so that the tissue is secured in its physiological condition, and then we dissected it. If we had done it the other way around, it wouldn’t have worked.”

と言っていて、普通は組織を解剖して取り出してから薬品に浸して固定するわけですが、それだと解剖の過程で生きたままの時の組織構造が破壊される可能性があるので、intracardial perfusionで血管を介して薬品を浸透させることで生きたままの時の組織構造を保存して、それを注意深く解剖して膜をとりだして観察したということです。

intracardial perfusion自体はとても良く使われる方法なのでべつに取り立てて珍しいこともないですが、彼のすごいところはさらに免疫細胞を染色して髄膜を観察したということです。免疫細胞?脳で?と思ってしまいましたがもともと多発性硬化症multiple sclerosisに注目して研究していたみたいです。

するとこのアントニーさんは、染色された免疫細胞の分布がなにか管に沿って分布しているように見えたのでリンパ系組織を染色(Lyve-1を発現しているlymphatic endothelial cellsを抗体で蛍光染色)してみたところ髄膜の中を走る血管と寄り添うように走っている細いリンパ管を発見したということです。

血管とあまりに近い位置にあるため見逃しやすいことと、先程いったようにintracardial perfusionで生きたままの時の組織構造を保存しないと免疫細胞の分布のパターンはおそらく失われる可能性が高いこと、リンパ系組織も染色しないと見えないことなどなど、いろいろな条件が揃わないと見逃してしまうような構造だったので350年も見つからずにここまで来たようです。

これはノーベル賞すぐそこ。数年で取れるんじゃないでしょうか。上に上げた悪性リンパ腫や多発性硬化症など脳に起こる免疫細胞が絡んだ疾患の治療に大きく貢献するであろうことは間違いありません。今まで常識はずれなのでだれもしなかったような実験がなされるようになるでしょう。

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