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While much attention has been given to ZIP14 and ZNT10, hepatic ZIP8 also plays a critical role in systemic Mn regulation

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

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

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

Determining if the EHBDs are involved is important as currently most research focuses on the liver parenchyma and the intrahepatic biliary tree without looking at the EHBD, which are known to be affected in the majority of PSC patients 6