ArticleThe Journal of biological chemistry2015
Pim-2 Kinase Influences Regulatory T Cell Function and Stability by Mediating Foxp3 Protein N-terminal Phosphorylation.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 84 citations in OpenAlex.
- Article
- Ustekinumab resistance in individuals with ulcerative colitis is associated with an alteration of a subset of proinflammatory mucosal regulatory T cells.Inflammatory bowel diseases · 2026Article
- Regulatory T cells in axial spondyloarthritis.Communications biology · 2026Review
- Targeting PIM2 improves antitumor immunity through promoting effector function and persistence of CD8 T cells.The Journal of clinical investigation · 2026Article
- Review
- Review
- Kinase signaling in the control of regulatory T cell function: molecular mechanisms and therapeutic implications.Frontiers in immunology · 2026Review
- Characterizing CSF inflammatory proteomics in pediatric post-hemorrhagic hydrocephalus and Anti-NMDAR encephalitis.Journal of neuroinflammation · 2025Article
- The Role of Ubiquitin-Proteasome System (UPS) in Asthma Pathology.Journal of asthma and allergy · 2025Review
- Reprogramming of regulatory T cells in inflammatory tumor microenvironment: can it become immunotherapy turning point?Frontiers in immunology · 2024Review
- Treg plasticity and human diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Review
- Development and function of FOXP3+ regulators of immune responses.Clinical and experimental immunology · 2023Article
- T cells in health and disease.Signal transduction and targeted therapy · 2023Review
- Review
- An overview of pim kinase as a target in multiple myeloma.Cancer medicine · 2023Review
- An XBP1s-PIM-2 positive feedback loop controls IL-15-mediated survival of natural killer cells.Science immunology · 2023Article
- Targeting post-translational modifications of Foxp3: a new paradigm for regulatory T cell-specific therapy.Frontiers in immunology · 2023Review
- Review
- PIM2 Expression Induced by Proinflammatory Macrophages Suppresses Immunotherapy Efficacy in Hepatocellular Carcinoma.Cancer research · 2022Article
- Role of PIM2 in acute lung injury induced by sepsis.Experimental and therapeutic medicine · 2022Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Regulation of the extent of immune responses is a requirement to maintain self-tolerance and limit inflammatory processes. CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells play a role in regulation. The Foxp3 transcription factor is considered a dominant regulator for Treg cell development and function. Foxp3 function itself is directly regulated by multiple posttranslational modifications that occur in response to various external stimuli. The Foxp3 protein is a component of several dynamic macromolecular regulatory complexes. The complexes change constituents over time and through different signals to regulate the development and function of regulatory T cells. Here we identified a mechanism regulating Foxp3 level and activity that operates through discrete phosphorylation. The Pim-2 kinase can phosphorylate Foxp3, leading to decreased suppressive functions of Treg cells. The amino-terminal domain of Foxp3 is modified at several sites by Pim-2 kinase. This modification leads to altered expression of proteins related to Treg cell functions and increased Treg cell lineage stability. Treg cell suppressive function can be up-regulated by either pharmacologically inhibiting Pim-2 kinase activity or by genetically knocking out Pim-2 in rodent Treg cells. Deficiency of Pim-2 activity increases murine host resistance to dextran sodium sulfate-induced colitis in vivo, and a Pim-2 small molecule kinase inhibitor also modified Treg cell functions. Our studies define a pathway for limiting the regulation of Foxp3 function because the Pim-2 kinase represents a potential therapeutic target for modulating the Treg cell suppressive activities in controlling immune responses.
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