A global view of T cell metabolism in systemic lupus erythematosus

Andrew Goetz, Joy Cagmat, Maigan Brusko, Todd M. Brusko, Anna Rushin, Matthew Merritt, Timothy Garrett, Laurence Morel, Purushottam Dixit

Research output: Contribution to journalArticlepeer-review

Abstract

Impaired metabolism is recognized as an important contributor to pathogenicity of T cells in Systemic Lupus Erythematosus (SLE). Over the last two decades, we have acquired significant knowledge about the signaling and transcriptomic programs related to metabolic rewiring in healthy and SLE T cells. However, our understanding of metabolic network activity derives largely from studying metabolic pathways in isolation. Here, we argue that enzymatic activities are necessarily coupled through mass and energy balance constraints with in-built network-wide dependencies and compensation mechanisms. Therefore, metabolic rewiring of T cells in SLE must be understood in the context of the entire network, including changes in metabolic demands such as shifts in biomass composition and cytokine secretion rates as well as changes in uptake/excretion rates of multiple nutrients and waste products. As a way forward, we suggest cell physiology experiments and integration of orthogonal metabolic measurements through computational modeling towards a comprehensive understanding of T cell metabolism in lupus.

Original languageEnglish (US)
Article number1371708
JournalFrontiers in immunology
Volume15
DOIs
StatePublished - 2024

Keywords

  • CD4 T cell
  • flux balance analysis
  • lupus
  • metabolic network
  • multiomic analyses

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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