The Role of Lipids in the Regulation of Immune Responses

Lipid metabolism plays a major role in the regulation of the immune system. Exogenous (dietary and microbial-derived) and endogenous (non-microbial-derived) lipids play a direct role in regulating immune cell activation, differentiation and expansion, and inflammatory phenotypes. Understanding the complexities of lipid–immune interactions may have important implications for human health, as certain lipids or immune pathways may be beneficial in circumstances of acute infection yet detrimental in chronic inflammatory diseases. Further, there are key differences in the lipid effects between specific immune cell types and location (e.g., gut mucosal vs. systemic immune cells), suggesting that the immunomodulatory properties of lipids may be tissue-compartment-specific, although the direct effect of dietary lipids on the mucosal immune system warrants further investigation. Importantly, there is recent evidence to suggest that lipid–immune interactions are dependent on sex, metabolic status, and the gut microbiome in preclinical models. While the lipid–immune relationship has not been adequately established in/translated to humans, research is warranted to evaluate the differences in lipid–immune interactions across individuals and whether the optimization of lipid–immune interactions requires precision nutrition approaches to mitigate or manage disease. In this review, we discuss the mechanisms by which lipids regulate immune responses and the influence of dietary lipids on these processes, highlighting compelling areas for future research.