Department of Biochemistry & Molecular Biology, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei, China; Department of Immunology, Bengbu Medical College, Bengbu, Anhui, China.
Scand J Immunol. 2014 Feb;79(2):98-104. doi: 10.1111/sji.12140.
Myeloid-derived suppressor cells (MDSCs), a heterogeneous population including myeloid progenitor and immature myeloid cells, are known to inhibit T cell responses. The issue of whether tumour-derived MDSCs regulate the immune response in an asthma environment is currently unclear. Here, we have reported that tumour-derived MDSCs shift the balance back to normal in a Th2-dominant asthmatic environment. In an ovalbumin (OVA)-induced mouse asthma model, injected tumour-derived MDSCs were recruited to the lungs of asthmatic mice by CC chemokine ligand 2 (CCL2). MDSCs transferred into asthmatic mice via i.v. injection suppressed the infiltration of inflammatory cells into the lung, the Th2 cytokine, IL-4, concentration in bronchial lavage fluid and the serum level of OVA-specific IgE. Increased TGF-β1 production in the lung was detected after transfer of MDSCs. The inhibitory effects of MDSCs were reversed upon treatment with an anti-TGF-β1 antibody, suggesting dependence of these activities on TGF-β1. Our findings imply that tumour-derived MDSCs inhibit the Th2 cell-mediated response against allergen in a TGF-β1-dependent manner. Based on the collective results, we propose that asthma may be effectively targeted using a novel MDSC-based cell therapy approach.
髓系来源的抑制性细胞（MDSCs）是一种异质性群体，包括髓系祖细胞和未成熟的髓系细胞，已知其可抑制 T 细胞的反应。目前尚不清楚肿瘤衍生的 MDSCs 是否在哮喘环境中调节免疫反应。在这里，我们报道了肿瘤衍生的 MDSCs 在 Th2 占优势的哮喘环境中将平衡转回正常。在卵清蛋白（OVA）诱导的小鼠哮喘模型中，注射的肿瘤衍生 MDSCs 通过 C 趋化因子配体 2（CCL2）募集到哮喘小鼠的肺部。通过静脉注射将 MDSCs 转移到哮喘小鼠中，可抑制炎症细胞浸润肺部、支气管肺泡灌洗液中 Th2 细胞因子 IL-4 浓度和 OVA 特异性 IgE 的血清水平。转移 MDSCs 后，在肺部检测到 TGF-β1 产生增加。用抗 TGF-β1 抗体治疗可逆转 MDSCs 的抑制作用，表明这些活性依赖于 TGF-β1。我们的研究结果表明，肿瘤衍生的 MDSCs 以 TGF-β1 依赖的方式抑制针对过敏原的 Th2 细胞介导的反应。基于这些结果，我们提出使用新型 MDSC 为基础的细胞治疗方法可能有效靶向哮喘。
