ArticleThe Journal of clinical investigation2016
RAC1 activation drives pathologic interactions between the epidermis and immune cells.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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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
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- An update on psoriasis and metabolic syndrome: A meta-analysis of observational studies.PloS one · 2017Pooled it
- TLR4-paxillin-Rac1 signaling mediates LPS-induced dysregulation of keratinocyte function.iScience · 2026Article
- Unrestrained MyD88 Signaling in A20-Deficient Keratinocytes Triggers T-Cell-Dependent Psoriatic Arthritis-Like Disease.The Journal of investigative dermatology · 2025Article
- Analysis of adverse drug reactions in 507 cases of Tislelizumab: A real-world retrospective study based on data from Guangxi, China.PloS one · 2025Article
- Discovery of a novel ROS-based signature for predicting prognosis and immunosuppressive tumor microenvironment in lung adenocarcinoma.Journal of Cancer · 2024Article
- Mind bomb 2 limits inflammatory dermatitis inPNAS nexus · 2024Article
- Lnc-HULC, miR-122, and sirtulin-1 as potential diagnostic biomarkers for psoriasis and their association with the development of metabolic syndrome during the disease course.Non-coding RNA research · 2023Article
- Review
- Targeting small GTPases: emerging grasps on previously untamable targets, pioneered by KRAS.Signal transduction and targeted therapy · 2023Review
- The E3 ubiquitin ligase MG53 inhibits hepatocellular carcinoma by targeting RAC1 signaling.Oncogenesis · 2022Article
- Mouse Models of Psoriasis: A Comprehensive Review.The Journal of investigative dermatology · 2022Review
- Germline biomarkers predict toxicity to anti-PD1/PDL1 checkpoint therapy.Journal for immunotherapy of cancer · 2022Article
- Advances in the pathogenesis of psoriasis: from keratinocyte perspective.Cell death & disease · 2022Review
- Transcriptional Analysis-Based Alterations Affecting Neuritogenesis of the Peripheral Nervous System in Psoriasis.Life (Basel, Switzerland) · 2022Article
- Skin Cancers and the Contribution of Rho GTPase Signaling Networks to Their Progression.Cancers · 2021Review
- Dysregulation of lncRNAs in autoimmune neuropathies.Scientific reports · 2021Article
- A computational multi-targeting approach for drug repositioning for psoriasis treatment.BMC complementary medicine and therapies · 2021Article
- Characterization of PCSK9 in the Blood and Skin of Psoriasis.The Journal of investigative dermatology · 2021Article
- Article
- Rac1, A Potential Target for Tumor Therapy.Frontiers in oncology · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 4 institutions in 3 countries.
Funding
Abstract
Interactions between the epidermis and the immune system govern epidermal tissue homeostasis. These epidermis-immune interactions are altered in the inflammatory disease psoriasis; however, the pathways that underlie this aberrant immune response are not well understood. Here, we determined that Ras-related C3 botulinum toxin substrate 1 (RAC1) is a key mediator of epidermal dysfunction. RAC1 activation was consistently elevated in psoriatic epidermis and primary psoriatic human keratinocytes (PHKCs) exposed to psoriasis-related stimuli, but not in skin from patients with basal or squamous cell carcinoma. Expression of a constitutively active form of RAC1 (RACV12) in mice resulted in the development of lesions similar to those of human psoriasis that required the presence of an intact immune system. RAC1V12-expressing mice and human psoriatic skin showed similar RAC1-dependent signaling as well as transcriptional overlap of differentially expressed epidermal and immune pathways. Coculture of PHKCs with immunocytes resulted in the upregulation of RAC1-dependent proinflammatory cytokines, an effect that was reproduced by overexpressing RAC1 in normal human keratinocytes. In keratinocytes, modulating RAC1 activity altered differentiation, proliferation, and inflammatory pathways, including STAT3, NFκB, and zinc finger protein 750 (ZNF750). Finally, RAC1 inhibition in xenografts composed of human PHKCs and immunocytes abolished psoriasiform hyperplasia and inflammation in vivo. These studies implicate RAC1 as a potential therapeutic target for psoriasis and as a key orchestrator of pathologic epidermis-immune interactions.
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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.