Metabolic Control of Th17 Cell Generation and CNS Inflammation.

Hongbo Chi Kai Yang

doi:10.4172/2155-9562.s12-004

Abstract

Multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system (CNS), results from uncontrolled auto reactive T cells that infiltrate the CNS and attack the myelin sheath. Th17 cells play a prominent role in the pathogenesis of MS and experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Extensive studies have focused on understanding the roles of cytokine signaling and transcriptional network in the differentiation of Th17 cells and their pathogenicity in CNS inflammation. Aside from these events, activated T cells dynamically reprogram their metabolic pathways to fulfill the bioenergic and biosynthetic requirements for proper T cell functions. Emerging evidence indicates that modulation of these metabolic pathways impinges upon the differentiation of Th17 cells and the pathogenesis of EAE. Thus, a better understanding of the functions and mechanisms of T cell metabolism in Th17 cell biology may provide new avenues for therapeutic targeting of MS. In this review, we discuss the recent advances in our understanding of T cell metabolic pathways involved in Th17 cell differentiation and CNS inflammation.

Highlights

To ensure proper electrical activity of neurons, the central nervous system (CNS) strictly controls immune cell entry across the bloodbrain barrier (BBB)
Blockade of glycolysis by HIF1α deletion or 2-DG treatment ameliorates the development of EAE [16,19]. These results demonstrate that HIF1αdependent glycolysis functions as a metabolic checkpoint for the differentiation of Th17 cells
These studies have led to the identification of the pivotal role of the IL-23/Th17/granulocytemacrophage colony-stimulating factor (GM-CSF) axis in the generation of pathogenic Th17 cells

Summary

Introduction

To ensure proper electrical activity of neurons, the central nervous system (CNS) strictly controls immune cell entry across the bloodbrain barrier (BBB). Modulation of specific metabolic pathways can suppress pathogenic T cell responses, for example, the differentiation of Th17 cells and EAE pathogenesis [16]. Aside from its role in T cell activation and proliferation, glucose metabolism impinges upon Th17 cell differentiation and the pathogenesis of EAE.

Results

Conclusion