MAP kinase phosphatase 2 deficient mice develop attenuated experimental autoimmune encephalomyelitis through regulating dendritic cells and T cells
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Abstract Mitogen-activated protein kinase phosphatases (MKPs) play key roles in inflammation and immune mediated diseases. Here we investigated the mechanisms by which MKP-2 modulates central nervous system (CNS) inflammation in experimental autoimmune encephalomyelitis (EAE). Our results show that MKP-2 mRNA levels in the spinal cord and lymphoid organs of EAE mice were increased compared with naive controls, indicating an important role for MKP-2 in EAE development. Indeed, MKP-2−/− mice developed reduced EAE severity, associated with diminished CNS immune cell infiltration, decreased proinflammatory cytokine production and reduced frequency of CD4+ and CD8+ T cells in spleens and lymph nodes. In addition, MKP-2−/− CD11c+ dendritic cells (DCs) had reduced expression of MHC-II and CD40 compared with MKP-2+/+ mice. Subsequent experiments revealed that CD4+ T cells from naïve MKP-2−/− mice had decreased cell proliferation and IL-2 and IL-17 production relative to wild type controls. Furthermore, co-culture experiments showed that bone marrow derived DCs of MKP-2−/− mice had impaired capability in antigen presentation and T cell activation. While MKP-2 also modulates macrophage activation, our study suggests that MKP-2 is essential to the pathogenic response of EAE, and it acts mainly via regulating the important antigen presenting DC function and T cell activation.
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Dusp4 null mice show impaired T cell activation.
“Dusp4 null mice show impaired T cell activation (83).”
From <i>Trem2</i> promotes anti-inflammatory responses in microglia and is suppressed under pro-inflammatory conditions (2020) · cites this paper as [83]
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- Authors
- Barbour, M., Plevin, R., & Jiang, H.-R.
- Affiliations
- University of Strathclyde (GB)
- Corresponding author
- Jiang, Hui-Rong
- Venue
- Scientific Reports
- Published
- 2016-12-13
- Volume
- 6
- Issue
- 1
- Pages
- 38999-38999
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5154199
- OpenAlex
- W2566058895
- Cited by
- 206
- References
- 35
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 2 · 2022: 1 · 2021: 99 · 2020: 55 · 2019: 20 · 2018: 11 · 2017: 13 · 2016: 3
- FWCI
- 14.22
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Strathprints: The University of Strathclyde institutional repository (University of Strathclyde) (acceptedVersion)
- Funders
- University of Strathclyde
- Wellcome Trust (089273/Z/09/Z, 089273)
- Engineering and Physical Sciences Research Council (EP/J500550/1)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- MKP-2, MAP kinase phosphatase, experimental autoimmune encephalomyelitis, dendritic cells, CD4+ T cells, CD8+ T cells, antigen presentation, T cell activation, MHC class II, CD40, inflammatory cytokines, macrophage activation, neuroinflammation
- MeSH terms
- Animals, Dendritic Cells, Encephalomyelitis, Autoimmune, Experimental, Interleukin-2, Lymphocyte Activation, CD4-Positive T-Lymphocytes, Protein Tyrosine Phosphatases, Mice, Knockout, CD8-Positive T-Lymphocytes, Interleukin-17, Mice
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