CD5 Deficiency Alters Helper T Cell Metabolic Function and Shifts the Systemic Metabolome

Kiara V Whitley; Claudia M Tellez Freitas; Carlos Moreno; Christopher Haynie; Joshua Bennett; John C Hancock; Tyler D Cox; Brett E Pickett; K Scott Weber

doi:10.3390/biomedicines10030704

CD5 Deficiency Alters Helper T Cell Metabolic Function and Shifts the Systemic Metabolome

Biomedicines. 2022 Mar 18;10(3):704. doi: 10.3390/biomedicines10030704.

Authors

Kiara V Whitley¹, Claudia M Tellez Freitas², Carlos Moreno¹, Christopher Haynie¹, Joshua Bennett¹, John C Hancock³, Tyler D Cox⁴, Brett E Pickett¹, K Scott Weber¹

Affiliations

¹ Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT 84602, USA.
² College of Dental Medicine, Roseman University of Health Sciences, South Jordan, UT 84095, USA.
³ Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
⁴ College of Osteopathic Medicine, Rocky Vista University, Ivins, UT 84738, USA.

Abstract

Metabolic function plays a key role in immune cell activation, destruction of foreign pathogens, and memory cell generation. As T cells are activated, their metabolic profile is significantly changed due to signaling cascades mediated by the T cell receptor (TCR) and co-receptors found on their surface. CD5 is a T cell co-receptor that regulates thymocyte selection and peripheral T cell activation. The removal of CD5 enhances T cell activation and proliferation, but how this is accomplished is not well understood. We examined how CD5 specifically affects CD4+ T cell metabolic function and systemic metabolome by analyzing serum and T cell metabolites from CD5WT and CD5KO mice. We found that CD5 removal depletes certain serum metabolites, and CD5KO T cells have higher levels of several metabolites. Transcriptomic analysis identified several upregulated metabolic genes in CD5KO T cells. Bioinformatic analysis identified glycolysis and the TCA cycle as metabolic pathways promoted by CD5 removal. Functional metabolic analysis demonstrated that CD5KO T cells have higher oxygen consumption rates (OCR) and higher extracellular acidification rates (ECAR). Together, these findings suggest that the loss of CD5 is linked to CD4+ T cell metabolism changes in metabolic gene expression and metabolite concentration.

Keywords: CD5; RNA-Seq; T cell co-receptor; T cell metabolism; bioinformatics; helper T cell; metabolomics.

Abstract

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