ArticleMucosal immunology2015
Dual-specificity phosphatase 6 regulates CD4+ T-cell functions and restrains spontaneous colitis in IL-10-deficient mice.
Article in Mucosal immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 49 citations in OpenAlex.
- The dual specificity phosphatase 2 act as distal regulatory node in T cell signaling.iScience · 2026Article
- Lipid nanoparticle mRNA delivery preserves CAR T cell cytotoxicity and limits exhaustion compared to electroporation.Molecular therapy. Nucleic acids · 2026Article
- DUSP family phosphatases in cell signaling, inflammation, and chronic diseases.Journal of biomedical science · 2026Review
- CD318 expression defines a novel subset of human CD8Science advances · 2026Article
- Interplay Between Dysregulated Immune System and the Footprints of Blood-Borne miRNAs in Treatment Naive Crohn's Disease and Ulcerative Colitis Patients.International journal of molecular sciences · 2025Article
- The deubiquitinase USP17LA negatively regulates T-cell activation and attenuates anti-tumor immunity.EMBO reports · 2025Article
- Article
- Applications of single-cell RNA sequencing in drug discovery and development.Nature reviews. Drug discovery · 2023Review
- T-helper cells flexibility: the possibility of reprogramming T cells fate.Frontiers in immunology · 2023Review
- Dusp6 deficiency attenuates neutrophil-mediated cardiac damage in the acute inflammatory phase of myocardial infarction.Nature communications · 2022Article
- Ferroptosis promotes T-cell activation-induced neurodegeneration in multiple sclerosis.Cellular & molecular immunology · 2022Article
- Targeting protein phosphatases for the treatment of inflammation-related diseases: From signaling to therapy.Signal transduction and targeted therapy · 2022Review
- Single-cell RNA sequencing uncovers the individual alteration of intestinal mucosal immunocytes iniScience · 2022Article
- Absent in Melanoma 2 (AIM2) Regulates the Stability of Regulatory T Cells.International journal of molecular sciences · 2022Article
- Short-Chain Fatty Acid Decreases the Expression of CEBPB to Inhibit miR-145-Mediated DUSP6 and Thus Further Suppresses Intestinal Inflammation.Inflammation · 2022Article
- Buffering Adaptive Immunity by Hydrogen Sulfide.Cells · 2022Review
- T cell receptor (TCR) signaling in health and disease.Signal transduction and targeted therapy · 2021Review
- Expression profiling of genes in rheumatoid fibroblast-like synoviocytes regulated by Fas ligand via cDNA microarray analysis.Experimental and therapeutic medicine · 2021Article
- BCI Suppresses RANKL-Mediated Osteoclastogenesis and Alleviates Ovariectomy-Induced Bone Loss.Frontiers in pharmacology · 2021Article
- Recent insights of T cell receptor-mediated signaling pathways for T cell activation and development.Experimental & molecular medicine · 2020Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Mitogen-activated protein kinase (MAPK) phosphatases are dual-specificity phosphatases (DUSPs) that dephosphorylate phosphothreonine and phosphotyrosine residues within MAPKs. DUSP6 preferentially dephosphorylates extracellular signal-regulated kinases 1 and 2 (ERK1/2) rendering them inactive. Here, we study the role of DUSP6 in CD4(+) T-cell function, differentiation, and inflammatory profile in the colon. Upon T-cell receptor (TCR) stimulation, DUSP6 knockout (Dusp6(-/-)) CD4(+) T cells showed increased ERK1/2 activation, proliferation, T helper 1 differentiation, and interferon-γ production, as well as a marked decrease in survival, interleukin- 17A (IL-17A) secretion, and regulatory T-cell function. To analyze the role of DUSP6 in vivo, we employed the Il10(-/-) model of colitis and generated Il10(-/-)/Dusp6(-/-) double-knockout mice. Il10(-/-)/Dusp6(-/-) mice suffered from accelerated and exacerbated spontaneous colitis, which was prevented by ERK1/2 inhibition. ERK1/2 inhibition also augmented regulatory T-cell differentiation in vitro and in vivo in both C57Bl/6 and Dusp6(-/-) mice. In summary, DUSP6 regulates CD4(+) T-cell activation and differentiation by inhibiting the TCR-dependent ERK1/2 activation. DUSP6 might therefore be a potential intervention target for limiting aberrant T-cell responses in T-cell-mediated diseases, such as inflammatory bowel disease.
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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.