Fatty Acid Metabolism and T Cells in Multiple Sclerosis

Abstract

Cellular metabolic remodeling is intrinsically linked to the development, activation, differentiation, function, and survival of T cells. T cells transition from a catabolic, naïve state to an anabolic effector state upon T cell activation. Subsequently, specialization of T cells into T helper (Th) subsets, including regulatory T cells (Treg), requires fine-tuning of metabolic programs that better support and optimize T cell functions for that particular environment. Increasingly, studies have shown that changes in nutrient availability at both the cellular and organismal level during disease states can alter T cell function, highlighting the importance of better characterizing metabolic-immune axes in both physiological and disease settings. In support of these data, a growing body of evidence is emerging that shows specific lipid species are capable of altering the inflammatory functional phenotypes of T cells. In this review we summarize the metabolic programs shown to support naïve and effector T cells, and those driving Th subsets. We then discuss changes to lipid profiles in patients with multiple sclerosis, and focus on how the presence of specific lipid species can alter cellular metabolism and function of T cells.

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“…Th17 cells, characterized by the expression of IL-17/IL-22 lineage cytokines and the master transcription factor RORγt, participate in type 3 immune responses to extracellular pathogens including some bacteria and fungi [ 85 ]. On the other hand, Treg cells regulate immune responses to maintain immune cell homeostasis and prevent immunopathology, rather than exerting effector functions like Th1/Th2/Th17 cells [ 86 , 87 ]. The function of cytotoxic T cells (CD8+ T cells) is to directly kill pathogen-infected and tumor cells [ 83 ].…”

“…into subgroups such as Th1, Th2, Th17, and Treg, all of which play important roles in immune regulation [81][82][83][84][85][86]. Th1 cells, characterized by the expression of interferon (IFN)-γ lineage cytokine and the master transcription factor T-bet, participate in type 1 immune responses to intracellular pathogens such as mycobacterial species and viruses [82].…”

Maladaptive T-Cell Metabolic Fitness in Autoimmune Diseases

“…A shift from the normal cholesterol biosynthesis pathway to a pathway that produces proinflammatory fatty acids has been observed in patients with MS. The longchain fatty acids (LCFAs) promote the production of IFN-γ and IL-17 that can exacerbate acute encephalitis, while short-chain fatty acids (SCFAs) exert protection by inducing Forkhead box P3 (FOXP3) expression and thus repressing the differentiation of Th17 subsets implicated in autoimmune reactions [32].…”