Metabolic Regulation of Innate Lymphoid Cell-Mediated Tissue Protection—Linking the Nutritional State to Barrier Immunity

Abstract

Innate lymphoid cells (ILC) are a recently described group of tissue-resident immune cells that play essential roles in maintaining and protecting the tissue barrier against invading pathogens. Extensive research has revealed that ILC-mediated immune responses are controlled by dietary components and metabolites. An additional role of ILC as important direct regulators of host metabolism and glucose tolerance is emerging. This suggests that ILC may act as key dietary sensors integrating nutritional and metabolic stress to facilitate both maintenance of barrier sites and a coordinated immune response protecting these tissues. In this respect, investigations have begun to determine how different ILC responses are metabolically fueled and the impact of nutrient availability on the regulation of ILC function. Here, we discuss the current literature concerning dietary and metabolic control of ILC. In particular, we address whether the dietary and metabolic control of ILC and their simultaneous influence on host metabolism may function as a coordinated program of barrier defense.

Hypoxia, Metabolism and Immune Cell Function

“…Innate lymphoid cells (ILCs) are a recently discovered immune cell type, which plays an important role in lymphoid organogenesis, epithelial tissue homeostasis and defense, as well in the amplification of inflammatory responses [ 105 , 170 ]. Group 1 ILCs includes conventional Natural Killer (NK) cells and non-NK cell ILC1, which are characterized based on their ability to produce INF-γ and TNF-α in response to stimulation with IL-12, IL-15, or IL-18, and expression of the transcription factors T-bet and EOMES [ 172 ]. They play an important role in promoting responses against intracellular pathogens such as Toxoplasma gondii [ 173 ].…”

“…In analogy to naïve human and murine T cells, resting NK cells predominantly use oxidative phosphorylation over aerobic glycolysis prior to activation [ 172 ]. Naïve NK cells possess limited requirements and they metabolize glucose through glycolysis coupled to oxidative phosphorylation to make ATP.…”

“…Upon long-term activation, murine and human NK cells rely on glucose metabolism via aerobic glycolysis in which they metabolize glucose into lactate [ 173 , 176 , 177 , 178 ]. IL2, produced by activated T cells, is the most important cytokine in activation of NK cells, which drives glycolytic reprogramming of both murine and human NK cells dependent on the mammalian target of rapamycin complex 1 (mTORC1) [ 172 , 173 , 176 , 178 ]. mTORC1 is a key regulator of immunological and metabolic responses, but the exact mechanism how mTORC1 regulates and controls NK cell metabolism is currently poorly understood.…”

Immunometabolism features of metabolic deregulation and cancer

“…Series of experiments showed that cholesterol synthesis pathway is essential for training of myeloid cells, which in turn are implicated in adiposeness and obesity . Furthermore, innate lymphoid cells (ILC) that are a group of tissue‐resident immune cells have been revealed to exert their vital functions through hosts dietary components and metabolites, which simultaneously affects host metabolism . In addition an intriguing view is presented by Paula Neto et al that food additives, which normally are considered harmless, can affect immune system cells that in turn modulates metabolic deregulations like obesity and diabetes.…”

“…9 Furthermore, innate lymphoid cells (ILC) that are a group of tissue-resident immune cells have been revealed to exert their vital functions through hosts dietary components and metabolites, which simultaneously affects host metabolism. 10 In addition an intriguing view is presented by Paula Neto et al 11 that food additives, which normally are considered harmless, can affect immune system cells that in turn modulates metabolic deregulations like obesity and diabetes. This notion is strengthened by the view that both immune disorders and abnormal metabolic states affect each other in bidirectional way, and more often than not immune activation leads to metabolically abnormal state which may be controlled by epigenetic mechanisms.…”