Components of the innate immune system such as macrophages and dendritic cells are instrumental in determining the fate of immune responses and are, also, among the most sensitive targets of early life environmental alterations including developmental immunotoxicity (DIT). DIT can impede innate immune cell maturation, disrupt tissue microenvironment, alter immune responses to infectious challenges, and disrupt regulatory responses. Dysregulation of inflammation, such as that observed with DIT, has been linked with an increased risk of chronic inflammatory diseases in both children and adults. In this review, we discuss the relationship between early-life risk factors for innate immune modulation and promotion of dysregulated inflammation associated with chronic inflammatory disease. The health risks from DIT-associated inflammation may extend beyond primary immune dysfunction to include an elevated risk of several later-life, inflammatory-mediated diseases that target a wide range of physiological systems and organs. For this reason, determination of innate immune status should be an integral part of drug and chemical safety evaluation.

中文翻译：

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炎症功能障碍和疾病中的早期生命环境和发育免疫毒性


先天免疫系统的组成部分，如巨噬细胞和树突状细胞，有助于确定免疫反应的命运，也是早期生命环境改变（包括发育免疫毒性（DIT））最敏感的目标之一。 DIT 可以阻碍先天免疫细胞成熟，破坏组织微环境，改变对感染挑战的免疫反应，并破坏调节反应。炎症失调（例如 DIT 观察到的炎症失调）与儿童和成人慢性炎症性疾病风险增加有关。在这篇综述中，我们讨论了先天免疫调节的早期危险因素与慢性炎症性疾病相关炎症失调的促进之间的关系。 DIT 相关炎症带来的健康风险可能不仅限于原发性免疫功能障碍，还包括多种针对多种生理系统和器官的晚年炎症介导疾病的风险升高。因此，先天免疫状态的测定应该成为药物和化学品安全性评价的一个组成部分。