Department of Internal Medicine and Clinical Immunology, Dijon University Hospital, Dijon, France.
Université Bourgogne Franche-Comté, INSERM, Etablissement Français du Sang, Bourgogne Franche-Comté (EFS BFC), UMR1098, RIGHT Interactions Greffon-Hôte-Tumeur/Ingénierie Cellulaire et Génique, Dijon, France.
Front Immunol. 2023 Feb 21;14:1137794. doi: 10.3389/fimmu.2023.1137794. eCollection 2023.
The pathogenesis of Giant Cell Arteritis (GCA) relies on vascular inflammation and vascular remodeling, the latter being poorly controlled by current treatments.
This study aimed to evaluate the effect of a novel cell therapy, Human Monocyte-derived Suppressor Cells (HuMoSC), on inflammation and vascular remodeling to improve GCA treatment. Fragments of temporal arteries (TAs) from GCA patients were cultured alone or in the presence of HuMoSCs or their supernatant. After five days, mRNA expression was measured in the TAs and proteins were measured in culture supernatant. The proliferation and migration capacity of vascular smooth muscle cells (VSMCs) were also analyzed with or without HuMoSC supernatant.
Transcripts of genes implicated in vascular inflammation (, , , ), vascular remodeling (, ), angiogenesis (VEGF) and extracellular matrix composition (, and ) were decreased in arteries treated with HuMoSCs or their supernatant. Likewise, concentrations of collagen-1 and VEGF were lower in the supernatants of TAs cultivated with HuMoSCs. In the presence of PDGF, the proliferation and migration of VSMCs were both decreased after treatment with HuMoSC supernatant. Study of the PDGF pathway suggests that HuMoSCs act through inhibition of mTOR activity. Finally, we show that HuMoSCs could be recruited in the arterial wall through the implication of CCR5 and its ligands.
Altogether, our results suggest that HuMoSCs or their supernatant could be useful to decrease vascular in flammation and remodeling in GCA, the latter being an unmet need in GCA treatment.
巨细胞动脉炎（GCA）的发病机制依赖于血管炎症和血管重塑，而后者目前的治疗方法难以控制。
本研究旨在评估一种新型细胞疗法，人单核细胞来源的抑制细胞（HuMoSC），对炎症和血管重塑的影响，以改善 GCA 的治疗效果。将 GCA 患者的颞动脉（TA）片段单独培养或在 HuMoSC 或其上清液存在的情况下培养。培养 5 天后，测量 TA 中的 mRNA 表达，并测量培养上清液中的蛋白质。还分析了有或没有 HuMoSC 上清液的血管平滑肌细胞（VSMC）的增殖和迁移能力。
血管炎症（、、、）、血管重塑（、）、血管生成（VEGF）和细胞外基质组成（、和）相关基因的转录物在 HuMoSC 或其上清液处理的动脉中减少。同样，在 HuMoSCs 培养的 TA 上清液中，胶原-1 和 VEGF 的浓度也较低。在 PDGF 存在的情况下，VSMC 的增殖和迁移在 HuMoSC 上清液处理后均减少。对 PDGF 通路的研究表明，HuMoSCs 通过抑制 mTOR 活性发挥作用。最后，我们表明 HuMoSCs 可以通过 CCR5 及其配体的参与而募集到动脉壁中。
总之，我们的研究结果表明，HuMoSC 或其上清液可能有助于减少 GCA 中的血管炎症和重塑，这是 GCA 治疗中的一个未满足的需求。
