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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorDomingo Bover, Sandra
dc.contributor.authorSolé Marce, Cristina
dc.contributor.authorMoline Marimon, Teresa
dc.contributor.authorFerrer Fabregas, Berta
dc.contributor.authorCortes Hernandez, Josefina
dc.date.accessioned2022-06-15T12:56:02Z
dc.date.available2022-06-15T12:56:02Z
dc.date.issued2021-12
dc.identifier.citationDomingo S, Solé C, Moliné T, Ferrer B, Cortés-Hernández J. Thalidomide Exerts Anti-Inflammatory Effects in Cutaneous Lupus by Inhibiting the IRF4/NF-ҡB and AMPK1/mTOR Pathways. Biomedicines. 2021 Dec;9(12):1857.
dc.identifier.issn2227-9059
dc.identifier.urihttp://hdl.handle.net/11351/7690
dc.descriptionCutaneous lupus; Mechanism of action; Thalidomide
dc.description.abstractThalidomide is effective in patients with refractory cutaneous lupus erythematosus (CLE). However, the mechanism of action is not completely understood, and its use is limited by its potential, severe side-effects. Immune cell subset analysis in thalidomide’s CLE responder patients showed a reduction of circulating and tissue cytotoxic T-cells with an increase of iNKT cells and a shift towards a Th2 response. We conducted an RNA-sequencing study using CLE skin biopsies performing a Therapeutic Performance Mapping System (TMPS) analysis in order to generate a predictive model of its mechanism of action and to identify new potential therapeutic targets. Integrating RNA-seq data, public databases, and literature, TMPS analysis generated mathematical models which predicted that thalidomide acts via two CRBN-CRL4A- (CRL4CRBN) dependent pathways: IRF4/NF-ҡB and AMPK1/mTOR. Skin biopsies showed a significant reduction of IRF4 and mTOR in post-treatment samples by immunofluorescence. In vitro experiments confirmed the effect of thalidomide downregulating IRF4 in PBMCs and mTOR in keratinocytes, which converged in an NF-ҡB reduction that led to a resolution of the inflammatory lesion. These results emphasize the anti-inflammatory role of thalidomide in CLE treatment, providing novel molecular targets for the development of new therapies that could avoid thalidomide’s side effects while maintaining its efficacy.
dc.language.isoeng
dc.publisherMDPI
dc.relation.ispartofseriesBiomedicines;9(12)
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceScientia
dc.subjectLupus eritematós - Tractament
dc.subjectMedicaments immunosupressors - Ús terapèutic
dc.subjectAvaluació de resultats (Assistència sanitària)
dc.subject.meshLupus Erythematosus, Cutaneous
dc.subject.mesh/drug therapy
dc.subject.meshImmunosuppressive Agents
dc.subject.meshTreatment Outcome
dc.titleThalidomide Exerts Anti-Inflammatory Effects in Cutaneous Lupus by Inhibiting the IRF4/NF-ҡB and AMPK1/mTOR Pathways
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.3390/biomedicines9121857
dc.subject.decslupus eritematoso cutáneo
dc.subject.decs/farmacoterapia
dc.subject.decsinmunosupresores
dc.subject.decsresultado del tratamiento
dc.relation.publishversionhttps://doi.org/10.3390/biomedicines9121857
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[Domingo S, Solé C, Cortés-Hernández J] Unitat de Lupus, Servei de Reumatologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Moliné T, Ferrer B] Servei de Patologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain
dc.identifier.pmid34944673
dc.identifier.wos000735571000001
dc.relation.projectidinfo:eu-repo/grantAgreement/ES/PE2013-2016/PI15%2F02145
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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