ArticleMolecular therapy : the journal of the American Society of Gene Therapy2024
PDIA3 orchestrates effector T cell program by serving as a chaperone to facilitate the non-canonical nuclear import of STAT1 and PKM2.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Gene expression regulation by CaCellular & molecular biology letters · 2026Pooled it
- PDIA6 exacerbates hepatocellular carcinoma via enhancing proteasome-dependent degradation of AKAP12.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- PDIA3 Inhibition Facilitates Sensitivity of IKE-Induced Ferroptosis via STAT3/LCN2 Axis to Improve Glioblastoma Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Simvastatin Alleviates ConA-Induced Autoimmune Hepatitis by Inhibiting CD4Inflammation · 2026Article
- Immunometabolic control of macrophage plasticity in wound healing: mechanistic insights and therapeutic opportunities.Frontiers in immunology · 2026Review
- Protein-protein interactions shape trans-regulatory impact of genetic variation on protein expression and complex traits.Nature genetics · 2026Article
- The beneficial effect of hepatic ER stress-associated protein PDI on obesity-associated glucose dysregulation.Nutrition & metabolism · 2025Article
- Nuclear PKM2: a signal receiver, a gene programmer, and a metabolic modulator.Journal of biomedical science · 2025Review
- Activation of HTR2B Suppresses Osteosarcoma Progression through the STAT1-NLRP3 Inflammasome Pathway and Promotes OASL1+ Macrophage Production to Enhance Antitumor Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- GDF15 orchestrates mitochondrial-immune crosstalk via SMAD7-HIF-1α-PKM2 cascade to attenuate septic liver injury.Frontiers in immunology · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
27 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dysregulated T cell activation underpins the immunopathology of rheumatoid arthritis (RA), yet the machineries that orchestrate T cell effector program remain incompletely understood. Herein, we leveraged bulk and single-cell RNA sequencing data from RA patients and validated protein disulfide isomerase family A member 3 (PDIA3) as a potential therapeutic target. PDIA3 is remarkably upregulated in pathogenic CD4 T cells derived from RA patients and positively correlates with C-reactive protein level and disease activity score 28. Pharmacological inhibition or genetic ablation of PDIA3 alleviates RA-associated articular pathology and autoimmune responses. Mechanistically, T cell receptor signaling triggers intracellular calcium flux to activate NFAT1, a process that is further potentiated by Wnt5a under RA settings. Activated NFAT1 then directly binds to the Pdia3 promoter to enhance the expression of PDIA3, which complexes with STAT1 or PKM2 to facilitate their nuclear import for transcribing T helper 1 (Th1) and Th17 lineage-related genes, respectively. This non-canonical regulatory mechanism likely occurs under pathological conditions, as PDIA3 could only be highly induced following aberrant external stimuli. Together, our data support that targeting PDIA3 is a vital strategy to mitigate autoimmune diseases, such as RA, in clinical settings.
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