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dc.contributor.authorAzzi, Jamilen_US
dc.contributor.authorThueson, Lindsayen_US
dc.contributor.authorMoore, Roberten_US
dc.contributor.authorAbdoli, Rozitaen_US
dc.contributor.authorReijonen, Helenaen_US
dc.contributor.authorAbdi, Rezaen_US
dc.date.accessioned2017-02-18T01:58:31Z
dc.date.issued2017en_US
dc.identifier.citationAzzi, Jamil, Lindsay Thueson, Robert Moore, Rozita Abdoli, Helena Reijonen, and Reza Abdi. 2017. “PI3Kγ Deficient NOD-Mice Are Protected from Diabetes by Restoring the Balance of Regulatory to Effector-T-Cells.” PLoS ONE 12 (1): e0169695. doi:10.1371/journal.pone.0169695. http://dx.doi.org/10.1371/journal.pone.0169695.en
dc.identifier.issn1932-6203en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:30371030
dc.description.abstractWith a steady increase in its incidence and lack of curative treatment, type 1 diabetes (T1D) has emerged as a major health problem worldwide. To design novel effective therapies, there is a pressing need to identify regulatory targets controlling the balance of autoreactive to regulatory-T-cells (Tregs). We previously showed that the inhibition of the γ-subunit of the Phosphoinositide-3-kinase (PI3K), significantly suppress autoimmune-diabetes. To further delineate the mechanisms and the selectivity of specific immune modulation by PI3Kγ-inhibition, we developed a new NOD mouse model of T1D lacking the γ-subunit of PI3K. Strikingly, the loss of PI3Kγ protected 92% of the NOD-mice from developing spontaneous diabetes. The NOD.PI3Kγ-/- mice are protected from insulitis secondary to a defect in CD4 and CD8 autoreactive-T-cells activation and survival. In addition, PI3Kγ-deficiency promoted Treg generation in-vitro and in-vivo. Furthermore, PI3Kγ-inhibitor (AS605240) inhibited proliferation and cytokine production of a human CD4+ T-cell clone specific for GAD555-567 peptide that was isolated from a patient with T1D. These studies demonstrate the key role of the PI3Kγ pathway in regulating autoimmune-diabetes and provide rationales for future devise of anti- PI3Kγ therapy in T1D.en
dc.language.isoen_USen
dc.publisherPublic Library of Scienceen
dc.relation.isversionofdoi:10.1371/journal.pone.0169695en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC5231340/pdf/en
dash.licenseLAAen_US
dc.subjectBiology and Life Sciencesen
dc.subjectCell Biologyen
dc.subjectCellular Typesen
dc.subjectAnimal Cellsen
dc.subjectBlood Cellsen
dc.subjectWhite Blood Cellsen
dc.subjectT Cellsen
dc.subjectImmune Cellsen
dc.subjectImmunologyen
dc.subjectMedicine and Health Sciencesen
dc.subjectEndocrinologyen
dc.subjectEndocrine Disordersen
dc.subjectDiabetes Mellitusen
dc.subjectMetabolic Disordersen
dc.subjectBiology and life sciencesen
dc.subjectCell biologyen
dc.subjectCellular typesen
dc.subjectAnimal cellsen
dc.subjectBlood cellsen
dc.subjectWhite blood cellsen
dc.subjectT cellsen
dc.subjectRegulatory T cellsen
dc.subjectImmune cellsen
dc.subjectMedicine and health sciencesen
dc.subjectCytotoxic T cellsen
dc.subjectPhysiologyen
dc.subjectImmune Physiologyen
dc.subjectCytokinesen
dc.subjectImmune Systemen
dc.subjectInnate Immune Systemen
dc.subjectDevelopmental Biologyen
dc.subjectMolecular Developmenten
dc.subjectCell Processesen
dc.subjectCell Deathen
dc.subjectApoptosisen
dc.subjectExperimental Organism Systemsen
dc.subjectModel Organismsen
dc.subjectMouse Modelsen
dc.subjectAnimal Modelsen
dc.subjectGastroenterology and Hepatologyen
dc.subjectBiliary Disordersen
dc.subjectInsulitisen
dc.titlePI3Kγ Deficient NOD-Mice Are Protected from Diabetes by Restoring the Balance of Regulatory to Effector-T-Cellsen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalPLoS ONEen
dash.depositing.authorAzzi, Jamilen_US
dc.date.available2017-02-18T01:58:31Z
dc.identifier.doi10.1371/journal.pone.0169695*
dash.contributor.affiliatedAbdi, Reza
dash.contributor.affiliatedAzzi, Jamil


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