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dc.contributor.authorMontes-Casado, Maria 
dc.contributor.authorOjeda, Gloria 
dc.contributor.authorCriado, Gabriel
dc.contributor.authorRojo, José M
dc.contributor.authorPortoles, Pilar 
dc.date.accessioned2022-04-08T11:09:24Z
dc.date.available2022-04-08T11:09:24Z
dc.date.issued2021-06-15
dc.identifier.citationInt J Mol Sci. 2021;22(12):6405.es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/13975
dc.description.abstractThe phosphatidylinositol 3-kinase (PI3K) family of enzymes plays a determinant role in inflammation and autoimmune responses. However, the implication of the different isoforms of catalytic subunits in these processes is not clear. Rheumatoid arthritis (RA) is a chronic, systemic autoimmune inflammatory disease that entails innate and adaptive immune response elements in which PI3K is a potential hub for immune modulation. In a mouse transgenic model with T-cell-specific deletion of p110α catalytic chain (p110α-/-ΔT), we show the modulation of collagen-induced arthritis (CIA) by this isoform of PI3K. In established arthritis, p110α-/-ΔT mice show decreased prevalence of illness than their control siblings, higher IgG1 titers and lower levels of IL-6 in serum, together with decreased ex vivo Collagen II (CII)-induced proliferation, IL-17A secretion and proportion of naive T cells in the lymph nodes. In a pre-arthritis phase, at 13 days post-Ag, T-cell-specific deletion of p110α chain induced an increased, less pathogenic IgG1/IgG2a antibodies ratio; changes in the fraction of naive and effector CD4+ subpopulations; and an increased number of CXCR5+ T cells in the draining lymph nodes of the p110α-/-ΔT mice. Strikingly, T-cell blasts in vitro obtained from non-immunized p110α-/-ΔT mice showed an increased expression of CXCR5, CD44 and ICOS surface markers and defective ICOS-induced signaling towards Akt phosphorylation. These results, plus the accumulation of cells in the lymph nodes in the early phase of the process, could explain the diminished illness incidence and prevalence in the p110α-/-ΔT mice and suggests a modulation of CIA by the p110α catalytic chain of PI3K, opening new avenues of intervention in T-cell-directed therapies to autoimmune diseases.es_ES
dc.description.sponsorshipThis research was funded by Acción Estratégica en Salud Intramural (AESI) del Instituto de Salud Carlos III, grant number AESI PI16CIII/00012 to PP, and by Acción Estratégica en Salud AESI del Instituto de Salud Carlos III, grant number AES PI16/00032 to G.C.es_ES
dc.language.isoenges_ES
dc.publisherMultidisciplinary Digital Publishing Institute (MDPI) es_ES
dc.type.hasVersionVoRes_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectCIAes_ES
dc.subjectCXCR5es_ES
dc.subjectClass I phosphoinositide-3 kinasees_ES
dc.subjectICOSes_ES
dc.subjectPI3Kes_ES
dc.subjectT celles_ES
dc.subjectArthritises_ES
dc.subjectP110αes_ES
dc.subjectSignalinges_ES
dc.titleThe PI-3-Kinase P110α Catalytic Subunit of T Lymphocytes Modulates Collagen-Induced Arthritises_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID34203838es_ES
dc.format.volume22es_ES
dc.format.number12es_ES
dc.format.page6405es_ES
dc.identifier.doi10.3390/ijms22126405es_ES
dc.contributor.funderInstituto de Salud Carlos III es_ES
dc.description.peerreviewedes_ES
dc.identifier.e-issn1422-0067es_ES
dc.relation.publisherversionhttps://doi.org/10.3390/ijms22126405es_ES
dc.identifier.journalInternational Journal of Molecular Scienceses_ES
dc.repisalud.centroISCIIIes_ES
dc.repisalud.institucionISCIIIes_ES
dc.rights.accessRightsopen accesses_ES
dc.relation.projectFISinfo:fis/Instituto de Salud Carlos III/Programa Estatal de Fomento de la Investigación Científica y Técnica de Excelencia/Subprograma Estatal de Generación de Conocimiento/ISCIII 2016 Modalidad Proyectos de Investigacion en Salud Intramurales. (2016)/PI16CIII/00012es_ES
dc.relation.projectFISinfo:fis/Instituto de Salud Carlos III/Programa Estatal de Fomento de la Investigación Científica y Técnica de Excelencia/Subprograma Estatal de Generación de Conocimiento/Proyectos de investigacion en salud (AES 2016). Modalidad proyectos en salud. (2016)/PI16/00032es_ES


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Atribución 4.0 Internacional
Este Item está sujeto a una licencia Creative Commons: Atribución 4.0 Internacional