Alterations of the IKZF1-IKZF2 tandem in immune cells of schizophrenia patients regulate associated phenotypes

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dc.contributor.authorBallasch, Iván
dc.contributor.authorLópez-Molina, Laura
dc.contributor.authorGalán-Ganga, Marcos
dc.contributor.authorSancho-Balsells, Anna
dc.contributor.authorRodríguez-Navarro, Irene
dc.contributor.authorBorràs-Pernas, Sara
dc.contributor.authorRabadán, M. Ángeles
dc.contributor.authorChen, Wanqi
dc.contributor.authorPastó-Pellicer, Carlota
dc.contributor.authorFlotta, Francesca
dc.contributor.authorMaoyu, Wang
dc.contributor.authorFernández Irigoyen, Joaquín
dc.contributor.authorSantamaría Martínez, Enrique
dc.contributor.authorAguilar, Ruth
dc.contributor.authorDobaño, Carlota
dc.contributor.authorEgri, Natalia
dc.contributor.authorHernández, Carla
dc.contributor.authorAlfonso, Miqueu
dc.contributor.authorJuan, Manel
dc.contributor.authorAlberch, Jordi
dc.contributor.authorToro, Daniel del
dc.contributor.authorArranz, Belén
dc.contributor.authorCanals, Josep M.
dc.contributor.authorGiralt, Albert
dc.contributor.departmentCiencias de la Saludes_ES
dc.contributor.departmentOsasun Zientziakeu
dc.date.accessioned2025-02-28T08:56:18Z
dc.date.available2025-02-28T08:56:18Z
dc.date.issued2024-12-18
dc.date.updated2025-02-28T08:37:38Z
dc.description.abstractSchizophrenia is a complex multifactorial disorder and increasing evidence suggests the involvement of immune dysregulations in its pathogenesis. We observed that IKZF1 and IKZF2, classic immune-related transcription factors (TFs), were both downregulated in patients' peripheral blood mononuclear cells (PBMCs) but not in their brain. We generated a new mutant mouse model with a reduction in Ikzf1 and Ikzf2 to study the impact of those changes. Such mice developed deficits in the three dimensions (positive-negative-cognitive) of schizophrenia-like phenotypes associated with alterations in structural synaptic plasticity. We then studied the secretomes of cultured PBMCs obtained from patients and identified potentially secreted molecules, which depended on IKZF1 and IKZF2 mRNA levels, and that in turn have an impact on neural synchrony, structural synaptic plasticity and schizophrenia-like symptoms in in vivo and in vitro models. Our results point out that IKZF1-IKZF2-dependent immune signals negatively impact on essential neural circuits involved in schizophrenia.en
dc.description.sponsorshipThis work was supported by grants from Ministerio de Ciencia e Innovaci\u00F3n/AEI/ https://doi.org/10.13039/501100011033 / and \u201CFEDER\u201D to A.G.: PID2021-122258OB-I00 and to J.A.: PID2020-119386RB-100 and from Instituto de Salud Carlos III (ISCIII): PI17/00246 to B.A. Our technician Ana L\u00F3pez, was supported by a Mar\u00EDa de Maeztu Unit of Excellence (Institute of Neurosciences, University of Barcelona, CEX2021-001159-M, Ministry of Science and Innovation). The project that gave rise to these results received the support of a fellowship from \u201Cla Caixa\u201D Foundation (ID 100010434). The fellowship code is LCF/BQ/DR21/11880016 to M.G.-G.
dc.format.mimetypeapplication/pdfen
dc.identifier.citationBallasch, I., López-Molina, L., Galán-Ganga, M., Sancho-Balsells, A., Rodríguez-Navarro, I., Borràs-Pernas, S., Rabadan, M. A., Chen, W., Pastó-Pellicer, C., Flotta, F., Maoyu, W., Fernández-Irigoyen, J., Santamaría, E., Aguilar, R., Dobaño, C., Egri, N., Hernandez, C., Alfonso, M., Juan, M., Alberch, J., Toro, D. del, Arranz, B., Canals, J. M., Giralt, A. (2024). Alterations of the IKZF1-IKZF2 tandem in immune cells of schizophrenia patients regulate associated phenotypes. Journal of Neuroinflammation, 21, 1-24. https://doi.org/10.1186/s12974-024-03320-3.
dc.identifier.doi10.1186/s12974-024-03320-3
dc.identifier.issn1742-2094
dc.identifier.urihttps://academica-e.unavarra.es/handle/2454/53606
dc.language.isoeng
dc.publisherBMC
dc.relation.ispartofJournal of Neuroinflammation (2024), vol. 21, núm. 326
dc.relation.projectIDinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-122258OB-I00/ES/
dc.relation.projectIDinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-119386RB-I00/ES/
dc.relation.projectIDinfo:eu-repo/grantAgreement/ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016 (ISCIII)/PI17%2F00246/ES/
dc.relation.publisherversionhttps://doi.org/10.1186/s12974-024-03320-3
dc.rights© The Author(s) 2024. This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectCCL5en
dc.subjectCognitive symptomsen
dc.subjectCXCL10en
dc.subjectHeliosen
dc.subjectIkarosen
dc.subjectIL-4en
dc.subjectLymphocytesen
dc.subjectMouse modelsen
dc.subjectNegative symptomsen
dc.subjectNeuronal networksen
dc.titleAlterations of the IKZF1-IKZF2 tandem in immune cells of schizophrenia patients regulate associated phenotypesen
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dspace.entity.typePublication
relation.isAuthorOfPublication86d1b76e-4790-40b1-a3ec-72331c5c6199
relation.isAuthorOfPublicationabacfd17-2b93-4d99-bae2-52053d57401e
relation.isAuthorOfPublication.latestForDiscovery86d1b76e-4790-40b1-a3ec-72331c5c6199

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