Cross-talk Between GM-CSF and LPS/TLR4 in the Generation of MDSC-like Cells

虽然过敏性哮喘通常被认为是一种儿童疾病，但它是一种慢性下呼吸道炎症状态，经常在以后的生活中被诊断出来。过敏性哮喘是由过敏原(S)和免疫系统之间的反复相互作用和哮喘疾病的性质加上老年人免疫功能的恶化而促进的，导致随着年龄的增长而增加诊断。此外，老龄化人口的症状往往更严重，导致治疗选择较少，对当前治疗干预措施的反应较差。我们实验室的最新结果表明，环境暴露内毒素与吸入细菌内毒素后肺内形成髓系抑制细胞(MDSCs)而建立对变应原的耐受性之间存在联系。这一发现是1989年提出的卫生学假说背后的一个潜在机制，该假说认为，接触与病原体相关的产品，如内毒素，可能会保护人们免受未来的过敏反应。遇到内毒素和抑制细胞形成之间的这种联系对于我们理解肺功能具有巨大的意义。重要的是，我们已经能够在过敏性炎症模型中使用这些抑制细胞(MDSCs)进行治疗。由于骨髓间充质干细胞可以通过GM-CSF和脂多糖的联合作用在体外产生，因此有很大的潜力对患者进行治疗干预，从而保证进一步研究这些细胞的生成和功能。

Although often thought of as a disease of childhood, allergic asthma is a chronic inflammatory condition of the lower airways that is frequently diagnosed later in life. Allergic asthma is promoted by repeated interactions between allergen(s) and the immune system and the nature of asthmatic disease combined with the deterioration of immune function in the elderly, results in increased diagnoses with age. Furthermore, symptoms are often worse in the aging population, resulting in fewer treatment options and poor response to current therapeutic interventions. Recent results from our laboratory suggest a connection between environmental exposure to endotoxin and the establishment of tolerance to allergens via the formation of myeloid-derived suppressor cells (MDSCs) in the lung following inhalation of bacterial endotoxin (lipopolysaccharide-LPS). This finding is a potential mechanism underlying the hygiene hypothesis, which was postulated in 1989, stating that exposure to pathogen-associated products, like endotoxin, may be protective against future allergic responses. This link between encounter with endotoxin and suppressor cell formation has huge implications for our understanding of pulmonary function. Importantly, we have been able to use these suppressor cells (MDSCs) therapeutically in a model of allergic inflammation. Because MDSCs can be generated in vitro by the combination of GM-CSF and LPS, there is great potential for therapeutic intervention on a patient-by-patient basis warranting further investigation of the generation and function of these cells.