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

Ballasch, Iván; López Molina, Laura; Galán Ganga, Marcos; Sancho Balsells, Anna; Rodriguez Navarro, Irene; Borràs Pernas, Sara; Rabadán Lozano, M. Ángeles; Chen, Wanqi; Pastó Pellicer, Carlota; Flotta, Francesca; Maoyu, Wang; Fernández Irigoyen, Joaquín; Santamaría Martínez, Enrique; Aguilar, Ruth; Dobaño, Carlota, 1969-; Egri, Natalia; Hernández, Carla; Alfonso, Miqueu; Juan, Manel; Alberch i Vié, Jordi, 1959-; Toro Ruiz, Daniel del; Arranz, Belén; Canals i Coll, Josep M.; Giralt Torroella, Albert

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

Schizophrenia 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 ce...

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Autores:	Ballasch, Iván, López Molina, Laura, Galán Ganga, Marcos, Sancho Balsells, Anna, Rodriguez Navarro, Irene, Borràs Pernas, Sara, Rabadán Lozano, M. Ángeles, Chen, Wanqi, Pastó Pellicer, Carlota, Flotta, Francesca, Maoyu, Wang, Fernández Irigoyen, Joaquín, Santamaría Martínez, Enrique, Aguilar, Ruth, Dobaño, Carlota, 1969-, Egri, Natalia, Hernández, Carla, Alfonso, Miqueu, Juan, Manel, Alberch i Vié, Jordi, 1959-, Toro Ruiz, Daniel del, Arranz, Belén, Canals i Coll, Josep M., Giralt Torroella, Albert
Tipo de recurso:	artículo
Estado:	Versión publicada
Fecha de publicación:	2024
País:	España
Institución:	Universidad de Barcelona
Repositorio:	Dipòsit Digital de la UB
OAI Identifier:	oai:diposit.ub.edu:2445/226872
Acceso en línea:	https://hdl.handle.net/2445/226872
Access Level:	acceso abierto
Palabra clave:	Esquizofrènia Psiconeuroimmunologia Psiquiatria biològica Schizophrenia Psychoneuroimmunology Biological psychiatry

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spelling	Alterations of the IKZF1-IKZF2 tandem in immune cells of schizophrenia patients regulate associated phenotypesBallasch, IvánLópez Molina, LauraGalán Ganga, MarcosSancho Balsells, AnnaRodriguez Navarro, IreneBorràs Pernas, SaraRabadán Lozano, M. ÁngelesChen, WanqiPastó Pellicer, CarlotaFlotta, FrancescaMaoyu, WangFernández Irigoyen, JoaquínSantamaría Martínez, EnriqueAguilar, RuthDobaño, Carlota, 1969-Egri, NataliaHernández, CarlaAlfonso, MiqueuJuan, ManelAlberch i Vié, Jordi, 1959-Toro Ruiz, Daniel delArranz, BelénCanals i Coll, Josep M.Giralt Torroella, AlbertEsquizofrèniaPsiconeuroimmunologiaPsiquiatria biològicaSchizophreniaPsychoneuroimmunologyBiological psychiatrySchizophrenia 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.BioMed Central2024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/226872Articles publicats en revistes (Biomedicina)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1186/s12974-024-03320-3Journal of Neuroinflammation, 2024, vol. 21, num.1https://doi.org/10.1186/s12974-024-03320-3cc-by-nc-nd (c) Ballasch, I. et al., 2024http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2268722026-05-27T06:46:51Z
dc.title.none.fl_str_mv	Alterations of the IKZF1-IKZF2 tandem in immune cells of schizophrenia patients regulate associated phenotypes
title	Alterations of the IKZF1-IKZF2 tandem in immune cells of schizophrenia patients regulate associated phenotypes
spellingShingle	Alterations of the IKZF1-IKZF2 tandem in immune cells of schizophrenia patients regulate associated phenotypes Ballasch, Iván Esquizofrènia Psiconeuroimmunologia Psiquiatria biològica Schizophrenia Psychoneuroimmunology Biological psychiatry
title_short	Alterations of the IKZF1-IKZF2 tandem in immune cells of schizophrenia patients regulate associated phenotypes
title_full	Alterations of the IKZF1-IKZF2 tandem in immune cells of schizophrenia patients regulate associated phenotypes
title_fullStr	Alterations of the IKZF1-IKZF2 tandem in immune cells of schizophrenia patients regulate associated phenotypes
title_full_unstemmed	Alterations of the IKZF1-IKZF2 tandem in immune cells of schizophrenia patients regulate associated phenotypes
title_sort	Alterations of the IKZF1-IKZF2 tandem in immune cells of schizophrenia patients regulate associated phenotypes
dc.creator.none.fl_str_mv	Ballasch, Iván López Molina, Laura Galán Ganga, Marcos Sancho Balsells, Anna Rodriguez Navarro, Irene Borràs Pernas, Sara Rabadán Lozano, M. Ángeles Chen, Wanqi Pastó Pellicer, Carlota Flotta, Francesca Maoyu, Wang Fernández Irigoyen, Joaquín Santamaría Martínez, Enrique Aguilar, Ruth Dobaño, Carlota, 1969- Egri, Natalia Hernández, Carla Alfonso, Miqueu Juan, Manel Alberch i Vié, Jordi, 1959- Toro Ruiz, Daniel del Arranz, Belén Canals i Coll, Josep M. Giralt Torroella, Albert
author	Ballasch, Iván
author_facet	Ballasch, Iván López Molina, Laura Galán Ganga, Marcos Sancho Balsells, Anna Rodriguez Navarro, Irene Borràs Pernas, Sara Rabadán Lozano, M. Ángeles Chen, Wanqi Pastó Pellicer, Carlota Flotta, Francesca Maoyu, Wang Fernández Irigoyen, Joaquín Santamaría Martínez, Enrique Aguilar, Ruth Dobaño, Carlota, 1969- Egri, Natalia Hernández, Carla Alfonso, Miqueu Juan, Manel Alberch i Vié, Jordi, 1959- Toro Ruiz, Daniel del Arranz, Belén Canals i Coll, Josep M. Giralt Torroella, Albert
author_role	author
author2	López Molina, Laura Galán Ganga, Marcos Sancho Balsells, Anna Rodriguez Navarro, Irene Borràs Pernas, Sara Rabadán Lozano, M. Ángeles Chen, Wanqi Pastó Pellicer, Carlota Flotta, Francesca Maoyu, Wang Fernández Irigoyen, Joaquín Santamaría Martínez, Enrique Aguilar, Ruth Dobaño, Carlota, 1969- Egri, Natalia Hernández, Carla Alfonso, Miqueu Juan, Manel Alberch i Vié, Jordi, 1959- Toro Ruiz, Daniel del Arranz, Belén Canals i Coll, Josep M. Giralt Torroella, Albert
author2_role	author author author author author author author author author author author author author author author author author author author author author author author
dc.subject.none.fl_str_mv	Esquizofrènia Psiconeuroimmunologia Psiquiatria biològica Schizophrenia Psychoneuroimmunology Biological psychiatry
topic	Esquizofrènia Psiconeuroimmunologia Psiquiatria biològica Schizophrenia Psychoneuroimmunology Biological psychiatry
description	Schizophrenia 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.
publishDate	2024
dc.date.none.fl_str_mv	2024
dc.type.none.fl_str_mv	info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion
format	article
status_str	publishedVersion
dc.identifier.none.fl_str_mv	https://hdl.handle.net/2445/226872
url	https://hdl.handle.net/2445/226872
dc.language.none.fl_str_mv	Inglés
language_invalid_str_mv	Inglés
dc.relation.none.fl_str_mv	Reproducció del document publicat a: https://doi.org/10.1186/s12974-024-03320-3 Journal of Neuroinflammation, 2024, vol. 21, num.1 https://doi.org/10.1186/s12974-024-03320-3
dc.rights.none.fl_str_mv	cc-by-nc-nd (c) Ballasch, I. et al., 2024 http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess
rights_invalid_str_mv	cc-by-nc-nd (c) Ballasch, I. et al., 2024 http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	application/pdf
dc.publisher.none.fl_str_mv	BioMed Central
publisher.none.fl_str_mv	BioMed Central
dc.source.none.fl_str_mv	Articles publicats en revistes (Biomedicina) reponame:Dipòsit Digital de la UB instname:Universidad de Barcelona
instname_str	Universidad de Barcelona
reponame_str	Dipòsit Digital de la UB
collection	Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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Alterations of the IKZF1-IKZF2 tandem in immune cells of schizophrenia patients regulate associated phenotypes

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