Chapman Timothy J, Georas Steve N
Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Rochester Medical Center, Rochester, NY 14610, United States.
Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Rochester Medical Center, Rochester, NY 14610, United States.
Int Immunopharmacol. 2014 Nov;23(1):330-6. doi: 10.1016/j.intimp.2014.05.033. Epub 2014 Jun 25.
The lung is constantly exposed to a variety of inhaled foreign antigens, many of which are harmless to the body. Therefore, the mucosal immune system must not only have the capacity to distinguish self from non-self, but also harmless versus dangerous non-self. To address this, mucosal immune cells establish an anti-inflammatory steady state in the lung that must be overcome by inflammatory signals in order to mount an effector immune response. In the case of inhaled allergens, the false detection of dangerous non-self results in inappropriate immune activation and eventual allergic asthma. Both basic and clinical studies suggest that the balance between tolerogenic and inflammatory immune responses is a key feature in the outcome of health or disease. This review is focused on what we term 'regulatory tone': the immunosuppressive environment in the lung that must be overcome to induce inflammatory responses. We will summarize the current literature on this topic, with a particular focus on the role of regulatory T cells in preventing allergic disease of the lung. We propose that inter-individual differences in regulatory tone have the potential to not only establish the threshold for immune activation in the lung, but also shape the quality of resulting effector responses following tolerance breakdown.
肺持续暴露于多种吸入性外来抗原，其中许多对身体无害。因此，黏膜免疫系统不仅必须具备区分自身与非自身的能力，还需区分无害的与危险的非自身。为解决这一问题，黏膜免疫细胞在肺中建立了一种抗炎稳态，炎症信号必须克服这种稳态才能引发效应性免疫反应。在吸入变应原的情况下，对危险非自身的错误检测会导致不适当的免疫激活并最终引发过敏性哮喘。基础研究和临床研究均表明，耐受性免疫反应与炎症性免疫反应之间的平衡是健康或疾病结局的关键特征。本综述聚焦于我们所称的“调节基调”：肺中必须被克服才能诱导炎症反应的免疫抑制环境。我们将总结关于这一主题的当前文献，特别关注调节性T细胞在预防肺部过敏性疾病中的作用。我们提出，调节基调的个体差异不仅有可能设定肺中免疫激活的阈值，还能在耐受性破坏后塑造所产生的效应性反应的质量。
