Immunometabolism: From basic mechanisms to translation

Abstract

Immunometabolism has emerged as a major mechanism central to adaptive and innate immune regulation. From early observations that inflammatory cytokines were induced in obese adipose tissue and that these cytokines contributed to metabolic disease, it was clear that metabolism and the immunological state are inextricably linked. With a second research wave arising from studies in cancer metabolism to also study the intrinsic metabolic pathways of immune cells themselves and how those pathways influence cell fate and function, immunometabolism is a rapidly maturing area of research. Several key themes and goals drive the field. There is abundant evidence that metabolic pathways are closely tied to cell signaling and differentiation which leads different subsets of immune cells to adopt unique metabolic programs specific to their state and environment. In this way, metabolic signaling drives cell fate. It is also apparent that microenvironment greatly influences cell metabolism. Immune cells adopt programs specific for the tissues where they infiltrate and reside. Ultimately, a central goal of the field is to apply immunometabolism findings to the discovery of novel therapeutic strategies in a wide range of diseases, including cancer, autoimmunity, and metabolic syndrome. This review summarizes these facets of immunometabolism and highlights opportunities for clinical translation.

Keywords: autoimmunity; immune-mediated diseases; infectious diseases; met.

FIGURE 1

Immunometabolism: From Basic Mechanisms to Translation—Graphical summary of reviews in this collection. This figure summarizes the series of reviews provided by experts in the field demonstrating the mechanisms of immunometabolism, impacts on certain tissues such as adipose tissue, and disease states such as inflammation, cancer, and lupus. ATM: adipose tissue macrophage; VAT: visceral adipose tissue; OXPHOS: oxidative phosphorylation

FIGURE 2

Metabolism regulates immune cell activation. Glycolytic metabolism in immune cells typically leads to activation of an effector phenotype (eg, effector T, M1-like macrophages, DC, NK, and B cells), whereas oxidative metabolism of substrates such as fatty acids (lipid) and amino acids including glutamine leads to a regulatory or memory phenotype. Immunometabolism is necessary for not only cellular energetics, but also contributes to biosynthetic intermediates and signaling