Developmental immunotoxicity (DIT) is a term given to encompass the environmentally induced disruption of normal immune development resulting in adverse outcomes. A myriad of chemical, physical, and psychological factors can all contribute to DIT. As a core component of the developmental origins of adult disease, DIT is interlinked with three important concepts surrounding health risks across a lifetime: (1) the Barker Hypothesis, which connects prenatal development to later-life diseases, (2) the hygiene hypothesis, which connects newborns and infants to risk of later-life diseases and, (3) fetal programming and epigenetic alterations, which may exert effects both in later life and across future generations. This review of DIT considers: (1) the history and context of DIT research, (2) the fundamental features of DIT, (3) the emerging role of DIT in risk of noncommunicable diseases (NCDs) and (4) the range of risk factors that have been investigated through human research. The emphasis on the human DIT-related literature is significant since most prior reviews of DIT have largely focused on animal research and considerations of specific categories of risk factors (e.g., heavy metals). Risk factors considered in this review include air pollution, aluminum, antibiotics, arsenic, bisphenol A, ethanol, lead (Pb), maternal smoking and environmental tobacco smoke, paracetamol (acetaminophen), pesticides, polychlorinated biphenyls, and polyfluorinated compounds. 1. Introduction Early-life environmental insults affecting the developing immune system can have significant health ramifications not only for the exposed offspring but also potentially extending to additional generations. Developmental immunotoxicity (DIT) appears to play a significant role in the current global epidemic of non-communicable diseases (NCDs) [1, 2]. This review of DIT begins with the history of DIT placed in the context of the area of immunology known as immunotoxicology and charts the emergence of recent concepts concerning early developmental programming as it impacts later-life health. It also describes the current state of the science for DIT and the likely applications of DIT assessment as it may impact both human health and environmental protection. In particular, the paper discusses (1) the history of DIT research, (2) the role of critical windows of vulnerability for the developing immune system, (3) frequent outcomes of DIT, (4) consideration of the microbiome in DIT, (5) the role of prenatal epigenetic alterations in immunotoxicity, and (6) the connection between DIT,
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