Pluripotent Stem Cell Model of Nakajo-Nishimura Syndrome Untangles Proinflammatory Pathways Mediated by Oxidative Stress.

ABSTRACT: Nakajo-Nishimura syndrome (NNS) is an immunoproteasome-associated autoinflammatory disorder caused by a mutation of the PSMB8 gene. Although dysfunction of the immunoproteasome causes various cellular stresses attributed to the overproduction of inflammatory cytokines and chemokines in NNS, the underlying mechanisms of the autoinflammation are still largely unknown. To investigate and understand the mechanisms and signal pathways in NNS, we established a panel of isogenic pluripotent stem cell (PSC) lines with PSMB8 mutation. Activity of the immunoproteasome in PSMB8-mutant PSC-derived myeloid cell lines (MT-MLs) was reduced even without stimulation compared with non-mutant-MLs. In addition, MT-MLs showed an overproduction of inflammatory cytokines and chemokines, with elevated reactive ox

SUBMITTER: Honda-Ozaki F 

PROVIDER: S-EPMC5989695 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature