ArticleJCI insight2019
Reciprocal regulation of Th2 and Th17 cells by PAD2-mediated citrullination.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- Role of the PADI family in inflammatory autoimmune diseases and cancers: A systematic review.Frontiers in immunology · 2023Pooled it
- NEMO (IKKγ) citrullination in microglia promotes neuroinflammation in the post-ischemic brain.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- The Role of Neutrophil Extracellular Traps (NETs) in the Pathogenesis of Ovarian Cancer: New Insight and Future Perspectives.Molecular biotechnology · 2026Review
- Regulation of basal and tumour necrosis factor α-induced fibroblast gene expression by peptidylarginine deiminase 2.The Journal of physiology · 2026Article
- Role of ITIH4 in Modulating YAP/TAZ-Mediated Apoptosis of Type II Alveolar Epithelium during Acute Respiratory Distress Syndrome.Pharmaceutical research · 2026Article
- NETs in ovarian cancer progression: innovative nanoparticle-based therapeutic strategies.European journal of medical research · 2025Review
- Peptidylarginine deiminase 2 contributes to pathogenesis in trinitrobenzenesulfonic acid-induced colitis through macrophage extracellular trap-independent pathways.Scientific reports · 2025Article
- Citrullination in tumor immunity and therapy.The Journal of clinical investigation · 2025Review
- Peptidylarginine Deiminase (PAD) Inhibitor Optimization through Displacement of a Trapped Water Molecule.ACS medicinal chemistry letters · 2025Article
- PAD2 disturbs cardiomyocyte calcium homeostasis by citrullinating SERCA2a protein in hemorrhagic shock induced arrhythmia.The journal of trauma and acute care surgery · 2025Article
- Inhibiting peptidylarginine deiminases (PAD1-4) by targeting a CaNature communications · 2025Article
- Citrullinated peptides as drug candidates for rheumatoid arthritis.Frontiers in immunology · 2025Review
- PAD4 controls tumor immunity via restraining the MHC class II machinery in macrophages.Cell reports · 2024Article
- The Role of Citrullination Modification in CD4Biomolecules · 2024Review
- Small molecule activates citrullination through targeting PAD2.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Article
- Therapeutic inhibition of CXCR1/2: where do we stand?Internal and emergency medicine · 2023Review
- PADs and NETs in digestive system: From physiology to pathology.Frontiers in immunology · 2023Review
- Peptidylarginine deiminase 2 citrullinates MZB1 and promotes the secretion of IgM and IgA.Frontiers in immunology · 2023Article
- Thinking outside the box: non-canonical targets in multiple sclerosis.Nature reviews. Drug discovery · 2022Review
- Microbial pathways to subvert host immunity generate citrullinated neoantigens targeted in rheumatoid arthritis.Current opinion in structural biology · 2022Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
Dysregulated citrullination, a unique form of posttranslational modification catalyzed by the peptidylarginine deiminases (PADs), has been observed in several human diseases, including rheumatoid arthritis. However, the physiological roles of PADs in the immune system are still poorly understood. Here, we report that global inhibition of citrullination enhances the differentiation of type 2 helper T (Th2) cells but attenuates the differentiation of Th17 cells, thereby increasing the susceptibility to allergic airway inflammation. This effect on Th cells is due to inhibition of PAD2 but not PAD4. Mechanistically, PAD2 directly citrullinates GATA3 and RORγt, 2 key transcription factors determining the fate of differentiating Th cells. Citrullination of R330 of GATA3 weakens its DNA binding ability, whereas citrullination of 4 arginine residues of RORγt strengthens its DNA binding. Finally, PAD2-deficient mice also display altered Th2/Th17 immune response and heightened sensitivity to allergic airway inflammation. Thus, our data highlight the potential and caveat of PAD2 as a therapeutic target of Th cell-mediated diseases.
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Registered trials
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.