肺線維症の発症におけるマクロファージの役割を探る新しい研究(New study probes macrophages’ role in developing pulmonary fibrosis)

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2024-04-11 バッファロー大学(UB)

マクロファージが肺線維症の病態形成に関与するメカニズムを解明するため、バッファロー大学の研究チームが、肺線維症患者の肺を模したミニチュアモデルを開発し、マクロファージと線維芽細胞、コラーゲン繊維の相互作用を調査しました。実験結果から、マクロファージは周囲の状況を感知し、瘢痕組織の成長を促進する生化学的要因を分泌することが明らかになりました。さらに、ピルフェニドンという薬剤は、マクロファージの働きを変化させ、瘢痕組織の形成を阻止することが示されました。

<関連情報>

肺線維症発症時のマクロファージの機械的活性化をモデル化し、抗線維症標的治療を目指す Modeling mechanical activation of macrophages during pulmonary fibrogenesis for targeted anti-fibrosis therapy

YING XU , LINXUAN YING, JENNIFER K. LANG, BORIS HINZ , AND RUOGANG ZHAO
Science Advances  Published:29 Mar 2024
DOI:https://doi.org/10.1126/sciadv.adj9559

Abstract

Pulmonary fibrosis is an often fatal lung disease. Immune cells such as macrophages were shown to accumulate in the fibrotic lung, but their contribution to the fibrosis development is unclear. To recapitulate the involvement of macrophages in the development of pulmonary fibrosis, we developed a fibrotic microtissue model with cocultured human macrophages and fibroblasts. We show that profibrotic macrophages seeded on topographically controlled stromal tissues became mechanically activated. The resulting co-alignment of macrophages, collagen fibers, and fibroblasts promoted widespread fibrogenesis in micro-engineered lung tissues. Anti-fibrosis treatment using pirfenidone disrupts the polarization and mechanical activation of profibrotic macrophages, leading to fibrosis inhibition. Pirfenidone inhibits the mechanical activation of macrophages by suppressing integrin αMβ2 and Rho-associated kinase 2. These results demonstrate a potential pulmonary fibrogenesis mechanism at the tissue level contributed by macrophages. The cocultured microtissue model is a powerful tool to study the immune–stromal cell interactions and the anti-fibrosis drug mechanism.

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