全身性強皮症は、皮膚を始め、内臓諸臓器に線維化・硬化をきたす結合織疾患である。その病態は、1) 免疫異常を背景に、2) 血管内皮細胞の障害をトリガーとして、最終的に、3) 活性化された線維芽細胞から、過剰な細胞外基質蛋白が産生され、局所に沈着する、という３つの側面から考えられている。主に、線維化を誘導する様々なサイトカイン、ケモカインの方面から、これまで研究がなされてきたが、強皮症研究は、他の膠原病に比べ遅れてきたと考えられてきた。その理由の一つに、適切な動物モデルが稀少であるということが挙げられる。

当科の山本が作成した強皮症モデルマウスは、強皮症研究のブレークスルーとなり、世界の強皮症研究に大きく貢献した。特徴は、方法が簡便で、短期間に、誰にでもでき、再現性が高いため、このモデルは、今や世界中で利用され、強皮症モデルというと、このモデルを指すまでになっている。他にも、遺伝子改変動物を利用したモデルなどはあるが、容易に作成でき、誰もが利用できるものはない。

このように強皮症研究は、病変部由来の線維芽細胞を使った、in vitroの研究と並行して、in vivoでの研究が進んだお蔭で、ここ数年飛躍的に病態解析は進んできた。この動物モデルは、強皮症の病態解明だけでなく、新たな治療法の開発にも寄与する。ただし、様々な治療薬の候補が研究されてはいるものの、未だに実用化されたものはほとんどないのが現状である。実際の患者さんへの治療という点では、まだまだ臨床現場へ還元できるには満足する結果ではない。引き続き、検討していく所存である。

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