ISG15 deficiency features a complex cellular phenotype that responds to treatment with itaconate and derivatives.

ABSTRACT:

Background

Congenital ISG15 deficiency is a rare autoinflammatory disorder that is driven by chronically elevated systemic interferon levels and predominantly affects central nervous system and skin.

Methods and results

We have developed induced pluripotent stem cell-derived macrophages and endothelial cells as a model to study the cellular phenotype of ISG15 deficiency and identify novel treatments. ISG15^-/- macrophages exhibited the expected hyperinflammatory responses, but normal phagocytic function. In addition, they displayed a multifaceted pathological phenotype featuring increased apoptosis/pyroptosis, oxidative stress, glycolysis, and acylcarnitine levels, but decreased glutamine uptake, BCAT1 expression, branched chain amino acid catabolism, oxidative pho

SUBMITTER: Waqas SF 

PROVIDER: S-EPMC9288839 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature