The Cellular and Molecular Basis of Translational Immunometabolism Giuseppe Danilo Norata, Giuseppina Caligiuri, Triantafyllos Chavakis, Giuseppe Matarese, Mihai Gheorge Netea, Antonino Nicoletti, Luke A.J. O’Neill, Federica M. Marelli-Berg  Immunity  Volume 43, Issue 3, Pages 421-434 (September 2015) DOI: 10.1016/j.immuni.2015.08.023 Copyright © 2015 Elsevier Inc. Terms and Conditions

Figure 1 Systemic to Cellular Immunometabolic Crosstalk Systemic metabolism, which is affected by the diet and gut microbiota, can contribute to immune system homeostasis by affecting the immune cell metabolic setup via nutrient availability and active metabolite-induced signaling, thus regulating their differentiation (1). Reprogramming of the metabolic configuration of immune cells can occur via epigenetic events also influenced by the metabolic microenvironment (2), thus opening a window of opportunity for therapeutic manipulation. Alteration of systemic metabolism due to dietetic overload or genetic defects (3) is associated with altered immune cell metabolism and the development of chronic inflammation and ineffective immunity (4). Immunity 2015 43, 421-434DOI: (10.1016/j.immuni.2015.08.023) Copyright © 2015 Elsevier Inc. Terms and Conditions

Figure 2 The Molecular and Translational Basis of Immunometabolism The profound integration of systemic and cellular metabolism suggests that therapeutic manipulation of systemic metabolism could re-establish immune homeostasis. The main challenge in translational immunometabolism is the identification of selective metabolic alterations in pathogenic immune cells and the definition of the molecular pathways selectively engaged by homeostatic metabolic immune cell phenotypes (effector versus regulatory) as an end point of immunometabolic therapies. Effective strategies might involve the following: (1) repositioning of existing (“old”) metabolic drugs, which, by improving homeostasis of metabolic organs (liver, adipose tissue, and pancreas), can divert metabolites to alternative routes and thus define systemic and cellular metabolic responses; and (2) reprogramming immune cells via epigenetic events and/or via the control of the metabolite milieu, as well as via modulating metabolic-dependent immune cell trafficking. Immunity 2015 43, 421-434DOI: (10.1016/j.immuni.2015.08.023) Copyright © 2015 Elsevier Inc. Terms and Conditions