Influence of Early-Life Environmental Exposures on Immune Function Across the Life Span

Abstract

As described in other chapters of this book, the function of the mature, fully formed immune system can be altered by a variety of environmental factors. While it is important to understand how these exposures modulate the immune system, an understudied aspect of how the environment shapes the immune system is the impact of exposures during development on the way the immune system functions later in life. Early life is a particularly susceptible time window for environmental exposures, because this is when the development and programming of multiple organs systems occurs (Nat Struct Mol Biol 20(3):282–289, 2013). In fact, some studies have shown that exposures during development lead to persistent changes in the function of other organ systems. Moreover, exposures during critical developmental periods lead to potentially permanent functional differences, as opposed to the generally transient changes that occurs after exposures during adulthood (Environ Health Perspect 120(10):1353–1361, 2012). Herein, we review the current evidence that the function of the immune system is sensitive to perturbation by developmental exposure to environmental agents. For some compounds, there is strong evidence that there are persistent immune defects associated with developmental exposures. For others, there are a handful of studies that suggest there may be immune consequences of developmental exposures. However, for many exposures little or nothing is known about whether developmental exposure has immunomodulatory effects that persist later in life. To provide an overview of current knowledge, we divide these exposures into five groups: pollutants for which a specific cellular receptor has been identified, smoke, heavy metals, pharmaceuticals, and maternal diet. Clearly, some of these agents contain a mixture of components, and metabolites of these agents may fall in to more than one category. Thus, in some situations the developing immune system is likely exposed to multiple environmental insults simultaneously. However, for brevity they are discussed in one place, acknowledging that these categories are not mutually exclusive.