Cellular metabolism regulates the differentiation and function of T-cell subsets

Cell Mol Immunol. 2024 May;21(5):419-435. doi: 10.1038/s41423-024-01148-8. Epub 2024 Apr 2.

Abstract

T cells are an important component of adaptive immunity and protect the host from infectious diseases and cancers. However, uncontrolled T cell immunity may cause autoimmune disorders. In both situations, antigen-specific T cells undergo clonal expansion upon the engagement and activation of antigens. Cellular metabolism is reprogrammed to meet the increase in bioenergetic and biosynthetic demands associated with effector T cell expansion. Metabolites not only serve as building blocks or energy sources to fuel cell growth and expansion but also regulate a broad spectrum of cellular signals that instruct the differentiation of multiple T cell subsets. The realm of immunometabolism research is undergoing swift advancements. Encapsulating all the recent progress within this concise review in not possible. Instead, our objective is to provide a succinct introduction to this swiftly progressing research, concentrating on the metabolic intricacies of three pivotal nutrient classes-lipids, glucose, and amino acids-in T cells. We shed light on recent investigations elucidating the roles of these three groups of metabolites in mediating the metabolic and immune functions of T cells. Moreover, we delve into the prospect of "editing" metabolic pathways within T cells using pharmacological or genetic approaches, with the aim of synergizing this approach with existing immunotherapies and enhancing the efficacy of antitumor and antiinfection immune responses.

Keywords: CD4+ T cells; CD8+T cells; Immunometabolism; Metabolism; T cell differentiation.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acids / metabolism
  • Animals
  • Cell Differentiation*
  • Energy Metabolism
  • Glucose / metabolism
  • Humans
  • T-Lymphocyte Subsets* / immunology
  • T-Lymphocyte Subsets* / metabolism

Substances

  • Glucose
  • Amino Acids