ArticleeLife2022
Redox regulation of PTPN22 affects the severity of T-cell-dependent autoimmune inflammation.
Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 22 citations in OpenAlex.
- Drugging the redox-regulated immunoproteome.Nature chemical biology · 2026Article
- Context‑dependent targeting of thioredoxin reductase 1 in cancer: a mechanistic review.Magyar onkologia · 2026Review
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- Deciphering the Immune Landscape of Abdominal Aortic Aneurysm: A Machine Learning and Cross-Species Validated Multi-Omics Approach.Journal of inflammation research · 2026Article
- Tolerogenic antigen-specific vaccine induces VISTA-enriched regulatory T cells and protects against arthritis in DRB1∗04:01 mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- A longitudinal cohort study uncovers plasma protein biomarkers predating clinical onset and treatment response of rheumatoid arthritis.Nature communications · 2025Article
- Harnessing Antioxidants in Cancer Therapy: Opportunities, Challenges, and Future Directions.Antioxidants (Basel, Switzerland) · 2025Review
- The systemic lupus erythematosus-associated NCF1Nature communications · 2025Article
- Human MHC Class II and Invariant Chain Knock-in Mice Mimic Rheumatoid Arthritis with Allele Restriction in Immune Response and Arthritis Association.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Redox Regulation of LAT Enhances T Cell-Mediated Inflammation.Antioxidants (Basel, Switzerland) · 2024Article
- Redox Regulation of Phosphatase and Tensin Homolog by Bicarbonate and Hydrogen Peroxide: Implication of Peroxymonocarbonate in Cell Signaling.Antioxidants (Basel, Switzerland) · 2024Article
- Regulation of T Cell Signaling and Immune Responses by PTPN22.Molecular and cellular biology · 2024Review
- Carbon dioxide/bicarbonate is required for sensitive inactivation of mammalian glyceraldehyde-3-phosphate dehydrogenase by hydrogen peroxide.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Redoxing PTPN22 activity.eLife · 2022Article
- Redox regulation of PTPN22 affects the severity of T-cell-dependent autoimmune inflammation.eLife · 2022Article
- The versatile utility of cysteine as a target for cancer treatment.Frontiers in oncology · 2022Review
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 8 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic autoimmune diseases are associated with mutations in PTPN22, a modifier of T cell receptor (TCR) signaling. As with all protein tyrosine phosphatases, the activity of PTPN22 is redox regulated, but if or how such regulation can modulate inflammatory pathways in vivo is not known. To determine this, we created a mouse with a cysteine-to-serine mutation at position 129 in PTPN22 (C129S), a residue proposed to alter the redox regulatory properties of PTPN22 by forming a disulfide with the catalytic C227 residue. The C129S mutant mouse showed a stronger T-cell-dependent inflammatory response and development of T-cell-dependent autoimmune arthritis due to enhanced TCR signaling and activation of T cells, an effect neutralized by a mutation in Ncf1, a component of the NOX2 complex. Activity assays with purified proteins suggest that the functional results can be explained by an increased sensitivity to oxidation of the C129S mutated PTPN22 protein. We also observed that the disulfide of native PTPN22 can be directly reduced by the thioredoxin system, while the C129S mutant lacking this disulfide was less amenable to reductive reactivation. In conclusion, we show that PTPN22 functionally interacts with Ncf1 and is regulated by oxidation via the noncatalytic C129 residue and oxidation-prone PTPN22 leads to increased severity in the development of T-cell-dependent autoimmunity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.