Show simple item record

 
dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorFissolo, Nicolás Miguel
dc.contributor.authorCalvo Barreiro, Laura
dc.contributor.authorEixarch Ahufinger, Herena
dc.contributor.authorBoschert, Ursula
dc.contributor.authorEspejo Ruiz, Carmen
dc.contributor.authorMontalban Gairín, Xavier
dc.contributor.authorComabella Lopez, Manuel
dc.date.accessioned2022-06-15T11:52:04Z
dc.date.available2022-06-15T11:52:04Z
dc.date.issued2021-12
dc.identifier.citationFissolo N, Calvo-Barreiro L, Eixarch H, Boschert U, Espejo C, Montalban X, et al. Immunomodulatory Effects Associated with Cladribine Treatment. Cells. 2021 Dec;10(12):3488.
dc.identifier.issn2073-4409
dc.identifier.urihttp://hdl.handle.net/11351/7685
dc.descriptionCladribine; Flow-cytometry; Multiple sclerosis
dc.description.abstractCladribine is a synthetic deoxyadenosine analogue with demonstrated efficacy in patients with relapsing-remitting multiple sclerosis (MS). The main mechanism of action described for cladribine is the induction of a cytotoxic effect on lymphocytes, leading to a long-term depletion of peripheral T and B cells. Besides lymphocyte toxicity, the mode of action may include immunomodulatory mechanisms affecting other cells of the immune system. In order to induce its beneficial effects, cladribine is phosphorylated inside the cell by deoxycytidine kinase (DCK) to its active form. However, the mechanism of action of cladribine may also include immunomodulatory pathways independent of DCK activation. This in vitro study was designed to explore the impact of cladribine on peripheral blood mononuclear cells (PBMC) subsets, and to assess whether the immunomodulatory mechanisms induced by cladribine depend on the activation of the molecule. To this end, we obtained PBMCs from healthy donors and MS patients and performed proliferation, apoptosis and activation assays with clinically relevant concentrations of cladribine in DCK-dependent and -independent conditions. We also evaluated the effect of cladribine on myeloid lineage-derived cells, monocytes and dendritic cells (DCs). Cladribine decreased proliferation and increased apoptosis of lymphocyte subsets after prodrug activation via DCK. In contrast, cladribine induced a decrease in immune cell activation through both DCK-dependent and -independent pathways (not requiring prodrug activation). Regarding monocytes and DCs, cladribine induced cytotoxicity and impaired the activation of classical monocytes, but had no effect on DC maturation. Taken together, these data indicate that cladribine, in addition to its cytotoxic function, can mediate immunomodulation in different immune cell populations, by regulating their proliferation, maturation and activation.
dc.language.isoeng
dc.publisherMDPI
dc.relation.ispartofseriesCells;10(12)
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceScientia
dc.subjectEsclerosi múltiple - Tractament
dc.subjectResposta immunitària - Regulació
dc.subjectCèl·lules - Proliferació
dc.subject.meshMultiple Sclerosis, Relapsing-Remitting
dc.subject.mesh/drug therapy
dc.subject.meshImmunomodulation
dc.subject.meshCell Proliferation
dc.titleImmunomodulatory Effects Associated with Cladribine Treatment
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.3390/cells10123488
dc.subject.decsesclerosis múltiple recurrente-remitente
dc.subject.decs/farmacoterapia
dc.subject.decsinmunomodulación
dc.subject.decsproliferación celular
dc.relation.publishversionhttps://doi.org/10.3390/cells10123488
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[Fissolo N, Calvo-Barreiro L, Eixarch H, Espejo C, Montalban X, Comabella M] Centre d’Esclerosi Múltiple de Catalunya (CEMCAT), Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Boschert U] Ares Trading, SA, 1262 Eysins, Switzerland. Merck KGaA, 64297 Darmstadt, Germany
dc.identifier.pmid34943995
dc.identifier.wos000736151100001
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


Files in this item

Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record