Immune Cell Function and Interaction
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Abstract
Abstract
ABSTRACT Amino acids play critical roles in the activation and function of lymphocytes. Here we show that the non-essential amino acid, asparagine, is essential for optimal activation and proliferation of CD4 + T cells. We demonstrate that asparagine depletion at different time points after CD4 + T cell activation reduces mitochondrial membrane potential and function. Furthermore, asparagine depletion at specific time points during CD4 + T cell differentiation reduces cytokine production in multiple CD4 + T cell subsets. In an adoptive transfer model of experimental autoimmune encephalomyelitis (EAE), myelin oligodendrocyte-specific pathogenic T helper 17 cells differentiated under Asn-deficient conditions exhibited reduced encephalitogenic potential and attenuated EAE severity. In a model of EAE induced by active immunization, therapeutic depletion of extracellular Asn significantly reduced disease severity. These results identify asparagine as a key metabolic regulator of the pathogenicity of autoreactive CD4 + T cells and suggest that targeting asparagine metabolism may be a novel therapeutic strategy for autoimmunity.
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@article{Georgiev2026Depletion,
title = {Depletion of extracellular asparagine impairs self-reactive T cells and ameliorates autoimmunity in a murine model of multiple sclerosis},
author = {Peter Georgiev and Sheila Johnson and Kiran Kurmi and Song-Hua Hu and SeongJun Han and Dillon G. Patterson and Thao H. Nguyen and Linglin Huang and Dan Liang and Naomi Goldman and Thomas S. Conway and Hannah Creasey and Jared H. Rowe and Marcia C. Haigis and Arlene H. Sharpe},
journal = {eLife},
year = {2026},
doi = {10.7554/elife.107745.3},
url = {https://doi.org/10.7554/elife.107745.3}
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