Role of Non‐codingRNAs in Innate Immune Responses Perturbed by Environmental Arsenic Exposure

Abstract

The innate immune system is essential for responding to different types of infections and injuries, and that response can be altered by environmental toxicants. Low-dose arsenic exposure can perturb and dysregulate the innate immune response. It is estimated that approximately 200 people worldwide are exposed to drinking water contaminated with arsenic. Low-dose arsenic exposure can lead to decreased innate immune function, but the mechanisms are not well understood. The zebrafish ( Danio rerio ) is a valuable vertebrate model for studying innate immune responses, as genes and pathways are highly conserved between zebrafish and humans. The zebrafish model has been used to study how toxicants, including arsenic, can dysregulate innate immune responses. Genetic regulators of the innate immune system include non-coding RNAs. Non-coding RNAs regulate innate immune pathways that modulate neutrophil and macrophage function. MicroRNAs are one class of non-coding RNAs that negatively regulate gene expression and have been shown to be differentially expressed after infection and arsenic exposure. Arsenic alters microRNA expression, including the function of macrophages and neutrophils, and subsequent disease susceptibility. Studies of non-coding RNAs in the context of gene-by-environment interactions offer the potential to gain new insight into the mechanisms of innate immune responses and into the toxicological effects of low-dose arsenic exposure.