Unlocking the Role of Exercise on CD4+ T Cell Plasticity.

Chloé D Goldsmith,David B Pyne,Nicole Vlahovich,Thomasina Donovan

doi:10.3389/fimmu.2021.729366

Abstract

A hallmark of T cell ageing is a loss of effector plasticity. Exercise delays T cell ageing, yet the mechanisms driving the effects of exercise on T cell biology are not well elucidated. T cell plasticity is closely linked with metabolism, and consequently sensitive to metabolic changes induced by exercise. Mitochondrial function is essential for providing the intermediate metabolites necessary to generate and modify epigenetic marks in the nucleus, thus metabolic activity and epigenetic mechanisms are intertwined. In this perspective we propose a role for exercise in CD4+ T cell plasticity, exploring links between exercise, metabolism and epigenetic reprogramming.

Highlights

Exercise can improve the efficacy of certain cancer therapies targeting kidney [1], bladder, testicular, and head and neck cancers [2]
CD4+ T cells include a diverse population with highly varied function
Plasticity is exhibited between CD4+ T cell subsets and linked to numerous maladies such as development and exacerbation of autoimmune disorders and tumorigenesis

Summary

INTRODUCTION

Exercise can improve the efficacy of certain cancer therapies targeting kidney [1], bladder, testicular, and head and neck cancers [2]. Whole genome mapping of permissive and repressive histone modifications in different CD4+ T cell lineages can reveal the presence of a mixed ‘poised’ state in the promoter of lineage‐ specific TFs. For example, in Th17 cells, the FOXP3 promoter is not epigenetically repressed, potentially allowing Th17 to Treg plasticity. In intestinal inflammation models Th17 cells can be highly plastic, developing a ‘Th1 like’ phenotype by expressing IFNG STAT4 and TBET, driving disease development [18] The phenotype of these pathogenic Th1 ex Th17 cells is associated with an increase in DNA methylation in IL17A locus, and a decrease in DNA methylation in TBX21 and IFNG [35]. The upstream factors responsible for driving epigenetic re-programming in T cells are not well understood

METABOLITES AND COFACTORS REQUIRED FOR EPIGENETIC MODIFICATIONS

CONCLUSIONS