Abstract Details

Title Cuproptosis May Contribute to NMOSD Pathogenesis by Skewing Naïve CD4+ T Cell Differentiation

Topic Autoimmune Neurology

Presentation(s) P6 - Poster Session 6 (5:00 PM-6:00 PM)

Poster/Presentation
Number 1-011

Objective To investigate the specific mechanism by which cuproptosis contributes to the pathogenesis of neuromyelitis optica spectrum disorder (NMOSD).

Background Our previous study (Liu et al. Sci Adv, 2025) suggested the potential of cuproptosis-related genes in predicting NMOSD relapse, yet the underlying mechanism remains unclear.

Design/Methods Peripheral blood samples were collected from NMOSD patients during acute and remission phases, and from healthy controls. PBMCs were isolated via Ficoll density gradient centrifugation. Naïve CD4+ T cells were purified using immunomagnetic beads. Single-cell RNA sequencing was performed, and data were analyzed with Seurat. Intracellular copper concentrations were quantified by a copper assay kit and LC-MS. Protein expression of the key cuproptosis regulator FDX1 was assessed by Western Blot. Naïve CD4+ T cells from healthy donors were cultured under pro-inflammatory (Th17/Tfh) polarizing conditions with or without the copper chelator tetrathiomolybdate (TTM). Final cell phenotypes were determined by flow cytometry.

Results Add Module Score analysis revealed a significant enrichment of cuproptosis-related genes in naïve CD4+ T cells from acute-phase NMOSD patients compared to both remission-phase patients and healthy controls. Consistently, these cells exhibited significantly elevated intracellular copper levels and FDX1 protein expression. In vitro, when healthy naïve CD4+ T cells were driven toward pro-inflammatory (Th17/Tfh) lineages, their endogenous copper and FDX1 levels increased. Crucially, copper chelation with TTM during polarization significantly reduced the generation of these pro-inflammatory T helper subsets.

Conclusions Our findings suggest that cuproptosis promotes NMOSD pathogenesis by driving the aberrant differentiation of naïve CD4+ T cells toward pro-inflammatory T helper cells. Targeting this pathway may represent a novel therapeutic strategy.

Authors/Disclosures
Hongbo Liu (the First Affiliated Hospital of Zhengzhou University, Zhengzhou University) PRESENTER	The institution of Hongbo Liu has received research support from China.
Peidong Liu	Dr. Liu has nothing to disclose.
Xinglin Wang, MD	No disclosure on file

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