Tissue Immunometabolism: Development, Physiology, and Pathobiology

Abstract

Evolution of metazoans resulted in the specialization of cellular and tissue function. This was accomplished by division of labor, which allowed tissue parenchymal cells to prioritize their core functions while ancillary functions were delegated to tissue accessory cells, such as immune, stromal, and endothelial cells. In metabolic organs, the accessory cells communicate with their clients, the tissue parenchymal cells, to optimize cellular processes, allowing organisms to adapt to changes in their environment. Here, we discuss tissue immunometabolism from this vantage point, and use examples from adipose tissues (white, beige, and brown) and liver to outline the general principles by which accessory cells support metabolic homeostasis in parenchymal cells. A corollary of this model is that disruption of communication between client and accessory cells might predispose metabolic organs to the development of disease.

Innate Lymphoid Cell Immunometabolism

“…These findings have been reviewed in detail previously[31]. Reciprocally, the immunometabolism field has also investigated how changes in local and systemic metabolism (often in metabolic disease settings) influence the immune system.…”

“…Metabolic tissues, such as the liver and adipose tissue, consist of stromal, parenchymal, and immune cells that coordinate their cellular functions to maintain the metabolic functions carried out by parenchymal cells (i.e hepatocytes and adipocytes). Immune and stromal populations are thought to maintain these functions through the production of various cytokines, growth factors, and hormones[31]. In addition, the immune system has evolved to be closely regulated by host nutritional status and environmental changes[31].…”

“…Immune and stromal populations are thought to maintain these functions through the production of various cytokines, growth factors, and hormones[31]. In addition, the immune system has evolved to be closely regulated by host nutritional status and environmental changes[31]. In this section, we will review studies demonstrating how ILCs influence tissue immunometabolism, and how environmental metabolic changes influence ILC biology.…”

“…Adipocytes also produce a plethora of secreted molecules called adipokines (i.e. leptin, resistin, and adiponectin) that maintain local and systemic tissue metabolic homeostasis[31]. A key characteristic of metabolic fitness of the adipose tissue is insulin sensitivity, which has been shown by several studies to be maintained by type 2 immune cells such as alternatively activated macrophages (M2), eosinophils, and Th2 cells[58–61].…”

“…Recent reports have identified certain ILC populations in non-barrier tissues with important host metabolic function (i.e. liver and adipose tissue) and collectively suggest a broader role for ILCs in the maintenance of both tissue homeostasis and systemic host metabolism[30, 31]. Given the contribution of ILCs to tissue inflammation in other diseases, it may not be surprising that recent studies have also implicated ILCs in the disruption of host tissue homeostasis and systemic metabolism during diet-induced obesity[13, 32–34].…”