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Even successful CAR T-cell therapy may fail to reverse established organ damage in autoimmune diseases, as demonstrated by SLE-related glomerulosclerosis, pulmonary fibrosis in systemic sclerosis, exocrine gland fibrosis in Sjgrens syndrome, and demyelinating lesions in multiple sclerosis

This leads to activation of protein kinase A and downstream transcriptional processes associated with growth hormone synthesis and release

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By directly testing whether activated neurons primarily oxidize astrocyte-derived lactate versus other substrates, and by accurately accounting for all sources of oxygen (vascular and extravascular), such approaches could provide definitive evidence to reconcile the conflicting models (Tietze, 1969

Supplementing NAD + enhances this immunostimulatory phenotype, while inhibiting mitochondrial respiration diminishes it 99