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Publication : Metabolic modulation of mitochondrial mass during CD4(+) T cell activation.

First Author  Kurmi K Year  2023
Journal  Cell Chem Biol Volume  30
Issue  9 Pages  1064-1075.e8
PubMed ID  37716347 Mgi Jnum  J:358184
Mgi Id  MGI:7779709 Doi  10.1016/j.chembiol.2023.08.008
Citation  Kurmi K, et al. (2023) Metabolic modulation of mitochondrial mass during CD4(+) T cell activation. Cell Chem Biol 30(9):1064-1075.e8
abstractText  Mitochondrial biogenesis initiates within hours of T cell receptor (TCR) engagement and is critical for T cell activation, function, and survival; yet, how metabolic programs support mitochondrial biogenesis during TCR signaling is not fully understood. Here, we performed a multiplexed metabolic chemical screen in CD4(+) T lymphocytes to identify modulators of metabolism that impact mitochondrial mass during early T cell activation. Treatment of T cells with pyrvinium pamoate early during their activation blocks an increase in mitochondrial mass and results in reduced proliferation, skewed CD4(+) T cell differentiation, and reduced cytokine production. Furthermore, administration of pyrvinium pamoate at the time of induction of experimental autoimmune encephalomyelitis, an experimental model of multiple sclerosis in mice, prevented the onset of clinical disease. Thus, modulation of mitochondrial biogenesis may provide a therapeutic strategy for modulating T cell immune responses.
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