Sex Differences in Immunometabolism: An Unexplored Area

The last three decades have seen a growing interest in research in the field of immunometabolism, likely because of promising discoveries made in this field. This includes demonstration of the crucial roles of cellular metabolism in the regulation of functional plasticity of various immune cells, their cross talk with major metabolic tissues (and consequently in the regulation of metabolic homeostasis) at the systemic level, and their potential in improving the efficacy of current immunotherapy or developing new therapeutics for a variety of metabolic and immune diseases (Lee YS, Wollam J, Olefsky JM, Cell 172:22-40, 2018). Surprisingly, sex differences, which are integral to metabolic and immune health and disease, have received a short shrift from researchers in this field. The purpose of this chapter in this protocols book in the Immunometabolism: Methods in Molecular Biology series is to bring attention to this understudied, but crucial, feature of immunometabolism within the scientific community. Sex differences in adipose (and by extension, metabolic) and immune functions are pervasive in metabolic and immune health and disease; it is likely that a better insight into them may open new research directions to better capitalize on the promising discoveries made in this field, and thereby contribute to the development of sex-based precision medicine. It is counterintuitive to ignore a fundamental aspect of immunometabolism, and thereby limit our ability to capitalize on its promising features in improving or maintaining health, and for the therapeutic targeting of associated diseases. Here we briefly discuss the potential drivers and touch upon some unanswered questions in sex differences in immunometabolism, especially those that require attention from the scientific community.