Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine, 3459 Fifth Avenue, MUH A628 NW, Pittsburgh, PA 15213, USA.
Immunol Res. 2011 Aug;50(2-3):153-8. doi: 10.1007/s12026-011-8230-1.
Myeloid-derived suppressor cells (MDSCs) have been investigated largely in the context of tumor progression. In contrast to the negative connotation of MDSCs in cancer immunity, our laboratory has recently reported on the development and role of pulmonary MDSC-like cells (CD11b(+)Gr1(int)F4/80(+)) in the regulation of allergic airway inflammation. These regulatory cells were expanded in a TLR4/MyD88-dependent manner and were both phenotypically and morphologically similar to those described in the tumor microenvironment. Although bacterial lipopolysaccharide (LPS) was initially described as an adjuvant in the development of allergic inflammation, subsequent studies showed that this is true only at relatively low doses of LPS. A high dose of LPS was shown to actually suppress eosinophilic airway inflammation. In our efforts to understand the mechanism underlying LPS-mediated suppression of allergic airway disease, we recently showed that LPS induces MDSC-like cells in the lung tissue in a dose-dependent manner, with increased accumulation of the cells at high doses of LPS. In contrast to lung dendritic cells (DCs), the MDSC-like cells did not traffic to the lung-draining lymph nodes, allowing them to act in a dominant fashion over DCs in the regulation of Th2 responses. The MDSC-like cells were found to blunt the ability of the lung DCs to upregulate GATA-3 or to promote STAT5 activation in primed Th2 cells, both transcription factors having critical roles in Th2 effector function. Thus, a complete understanding of the generation and regulation of the lung MDSCs would provide novel options for therapeutic interventions.
髓源抑制性细胞（MDSCs）在肿瘤进展的背景下得到了广泛研究。与 MDSCs 在癌症免疫中的负面含义形成对比的是，我们实验室最近报道了肺部 MDSC 样细胞（CD11b(+)Gr1(int)F4/80(+)）在调节过敏性气道炎症中的发展和作用。这些调节性细胞以 TLR4/MyD88 依赖性的方式扩增，在表型和形态上都与肿瘤微环境中描述的细胞相似。尽管细菌脂多糖（LPS）最初被描述为过敏性炎症发展中的佐剂，但随后的研究表明，这仅在 LPS 的相对低剂量下才是正确的。高剂量的 LPS 实际上被证明可以抑制嗜酸性气道炎症。在我们努力理解 LPS 介导的过敏性气道疾病抑制的机制的过程中，我们最近表明 LPS 以剂量依赖性的方式在肺部组织中诱导 MDSC 样细胞，并且在高剂量 LPS 时细胞的积累增加。与肺部树突状细胞（DCs）不同，MDSC 样细胞不会向肺部引流淋巴结迁移，使它们在调节 Th2 反应方面以优势方式作用于 DCs。发现 MDSC 样细胞削弱了肺部 DC 上调 GATA-3 或促进已被激活的 Th2 细胞中 STAT5 激活的能力，这两种转录因子在 Th2 效应功能中都具有关键作用。因此，对肺部 MDSC 的产生和调节的全面理解将为治疗干预提供新的选择。
