ArticleProceedings of the National Academy of Sciences of the United States of America2012
Cell type-specific targeting dissociates the therapeutic from the adverse effects of protein kinase inhibition in allergic skin disease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- Programming Brain Cell-Type-Selective Delivery In Vivo with Transporter-Guided Therapeutics.bioRxiv : the preprint server for biology · 2026Article
- Gene, cell type, and drug prioritization analysis suggest genetic basis for the utility of diuretics in treating Alzheimer disease.HGG advances · 2023Article
- The kinase p38α functions in dendritic cells to regulate Th2-cell differentiation and allergic inflammation.Cellular & molecular immunology · 2022Article
- The Developmental Transcription Factor p63 Is Redeployed to Drive Allergic Skin Inflammation through Phosphorylation by p38α.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Immune-Regulatory and Molecular Effects of Antidepressants on the Inflamed Human Keratinocyte HaCaT Cell Line.Neurotoxicity research · 2021Article
- The sex-specific role of p38 MAP kinase in CNS autoimmunity is regulated by estrogen receptor alpha.Journal of neuroimmunology · 2020Article
- p38α has an important role in antigen cross-presentation by dendritic cells.Cellular & molecular immunology · 2018Article
- p38γ and p38δ Are Involved in T Lymphocyte Development.Frontiers in immunology · 2018Article
- Anti-inflammatory roles of p38α MAPK in macrophages are context dependent and require IL-10.Journal of leukocyte biology · 2017Article
- Selenoprotein MsrB1 promotes anti-inflammatory cytokine gene expression in macrophages and controls immune response in vivo.Scientific reports · 2017Article
- Loss of Functionally Redundant p38 Isoforms in T Cells Enhances Regulatory T Cell Induction.The Journal of biological chemistry · 2017Article
- Keratinocyte p38δ loss inhibits Ras-induced tumor formation, while systemic p38δ loss enhances skin inflammation in the early phase of chemical carcinogenesis in mouse skin.Molecular carcinogenesis · 2016Article
- Loss of epidermal p38α signaling prevents UVR-induced inflammation via acute and chronic mechanisms.The Journal of investigative dermatology · 2014Article
- The emerging role of p38 mitogen-activated protein kinase in multiple sclerosis and its models.Molecular and cellular biology · 2013Review
- Activation of p38α in T cells regulates the intestinal host defense against attaching and effacing bacterial infections.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- Tuning of protein kinase circuitry by p38α is vital for epithelial tissue homeostasis.The Journal of biological chemistry · 2013Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 4 countries.
Funding
Abstract
The kinase p38α, originally identified because of its endotoxin- and cytokine-inducible activity and affinity for antiinflammatory compounds, has been posited as a promising therapeutic target for various immune-mediated disorders. In clinical trials, however, p38α inhibitors produced adverse skin reactions and other toxic effects that often outweighed their benefits. Such toxicity may arise from a perturbation of physiological functions unrelated to or even protective against the disease being treated. Here, we show that the effect of interfering with p38α signaling can be therapeutic or adverse depending on the targeted cell type. Using a panel of mutant mice devoid of p38α in distinct cell types and an experimental model of allergic skin disease, we find that dendritic cell (DC)-intrinsic p38α function is crucial for both antigen-specific T-cell priming and T-cell-mediated skin inflammation, two independent processes essential for the immunopathogenesis. By contrast, p38α in other cell types serves to prevent excessive inflammation or maintain naïve T-cell pools in the peripheral lymphoid tissues. These findings highlight a dilemma in the clinical use of p38α inhibitors, yet also suggest cell-selective targeting as a potential solution for improving their therapeutic index.
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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.