ArticleEMBO molecular medicine2022
Allosteric inhibition of SHP2 uncovers aberrant TLR7 trafficking in aggravating psoriasis.
Article in EMBO molecular medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
38 citing papers in PubMed, 66 citations in OpenAlex.
- Beyond polarization: a receptor-centered framework for macrophage function and therapy in skin diseases.Clinical and experimental medicine · 2026Review
- DGAT1 regulates keratinocyte proliferation through the modulation of retinoid homeostasis.Journal of physiology and biochemistry · 2026Article
- Dissecting the role of imiquimod and isostearic acid in Aldara-induced psoriasis mouse model.JID innovations : skin science from molecules to population health · 2026Article
- Advances in the application of spatial transcriptomics in understanding development and disease.Molecular and cellular biochemistry · 2026Review
- Targeting KAT8 alleviates self-RNA-driven skin inflammation by modulating histone H4 lysine 16 acetylation in psoriasis.Cell death and differentiation · 2026Article
- Hibiscetin-Loaded Nanogel Ameliorated the Severity of IMQ-Induced Psoriasis-Like Inflammation in Mice via Down-Regulating Interleukins/TNF-α/NF-κB.Journal of inflammation research · 2026Article
- Toll-like receptors in innate immunity and inflammation: from fundamental biology to clinic insights.Immunity & inflammation · 2026Review
- The multifaceted role of NF-κB signaling in psoriasis: from inflammatory amplification to epidermal remodeling.Frontiers in immunology · 2026Review
- A review of core immuno-inflammatory mechanisms and key regulatory targets in psoriasis.American journal of clinical and experimental immunology · 2026Review
- Single-Cell RNA Sequencing Revealing Dysregulated Perturbations of Tregs in Psoriasis and Construction of a Treg-Related Diagnostic Model via a 101- Combination Machine Learning Computational FrameworkEndocrine, metabolic & immune disorders drug targets · 2026Article
- The role of the striatin family proteins in hippo signaling and cellular regulation.Cell & bioscience · 2025Article
- Article
- Emerging Techniques in Spatial Multiomics: Fundamental Principles and Applications to Dermatology.The Journal of investigative dermatology · 2025Review
- Psoriasis: A Multidimensional Review of Onset, Progression, Treatment, and the Evolution of Disease Models.Molecular diagnosis & therapy · 2025Review
- Techniques and analytic workflow for spatial transcriptomics and its application to allergy and inflammation.The Journal of allergy and clinical immunology · 2025Review
- Celastrol directly targets LRP1 to inhibit fibroblast-macrophage crosstalk and ameliorates psoriasis progression.Acta pharmaceutica Sinica. B · 2025Article
- Protein phosphatases in systemic autoimmunity.Immunometabolism (Cobham, Surrey) · 2025Review
- SHP2 inhibition by SHP099 attenuates IL-6-driven osteoclastogenesis in growth plate injury.Frontiers in immunology · 2025Article
- SHP2-Triggered Endothelial Cell Activation Fuels Estradiol-Independent Endometrial Sterile Inflammation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Macrophage P2YActa pharmaceutica Sinica. B · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Psoriasis is a complex chronic inflammatory skin disease with unclear molecular mechanisms. We found that the Src homology-2 domain-containing protein tyrosine phosphatase-2 (SHP2) was highly expressed in both psoriatic patients and imiquimod (IMQ)-induced psoriasis-like mice. Also, the SHP2 allosteric inhibitor SHP099 reduced pro-inflammatory cytokine expression in PBMCs taken from psoriatic patients. Consistently, SHP099 significantly ameliorated IMQ-triggered skin inflammation in mice. Single-cell RNA sequencing of murine skin demonstrated that SHP2 inhibition impaired skin inflammation in myeloid cells, especially macrophages. Furthermore, IMQ-induced psoriasis-like skin inflammation was significantly alleviated in myeloid cells (monocytes, mature macrophages, and granulocytes)-but not dendritic cells conditional SHP2 knockout mice. Mechanistically, SHP2 promoted the trafficking of toll-like receptor 7 (TLR7) from the Golgi to the endosome in macrophages by dephosphorylating TLR7 at Tyr1024, boosting the ubiquitination of TLR7 and NF-κB-mediated skin inflammation. Importantly, Tlr7 point-mutant knock-in mice showed an attenuated psoriasis-like phenotype compared to wild-type littermates following IMQ treatment. Collectively, our findings identify SHP2 as a novel regulator of psoriasis and suggest that SHP2 inhibition may be a promising therapeutic approach for psoriatic patients.
Indexed as
Identifiers
What OpenQuestion holds
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.