Please use this identifier to cite or link to this item: http://hdl.handle.net/11452/28838
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dc.contributor.authorMa, Cindy S.-
dc.contributor.authorWong, Natalie-
dc.contributor.authorRao, Geetha-
dc.contributor.authorNguyen, Akira-
dc.contributor.authorAvery, Danielle T.-
dc.contributor.authorPayne, Kathryn-
dc.contributor.authorTorpy, James-
dc.contributor.authorO'Young, Patrick-
dc.contributor.authorDeenick, Elissa-
dc.contributor.authorBustamante, Jacinta-
dc.contributor.authorPuel, Anne-
dc.contributor.authorOkada, Satoshi-
dc.contributor.authorKobayashi, Masao-
dc.contributor.authorMartinez-Barricarte, Ruben-
dc.contributor.authorElliott, Michael-
dc.contributor.authorEl Baghdadi, Jamila-
dc.contributor.authorMinegishi, Yoshiyuki-
dc.contributor.authorBousfiha, Aziz-
dc.contributor.authorRobertson, Nic-
dc.contributor.authorHambleton, Sophie-
dc.contributor.authorArkwright, Peter D.-
dc.contributor.authorFrench, Martyn-
dc.contributor.authorBlincoe, Annaliesse K.-
dc.contributor.authorHsu, Peter-
dc.contributor.authorCampbell, Dianne E.-
dc.contributor.authorStormon, Michael O.-
dc.contributor.authorWong, Melanie-
dc.contributor.authorAdelstein, Stephen-
dc.contributor.authorFulcher, David A.-
dc.contributor.authorCook, Matthew C.-
dc.contributor.authorStepensky, Polina-
dc.contributor.authorBoztuğ, Kaan-
dc.contributor.authorBeier, Rita-
dc.contributor.authorİkincioğulları, Aydan-
dc.contributor.authorZiegler, John B.-
dc.contributor.authorGray, Paul-
dc.contributor.authorPicard, Capucine-
dc.contributor.authorBoisson-Dupuis, Stephanie-
dc.contributor.authorTri Giang, Phan-
dc.contributor.authorGrimbacher, Bodo-
dc.contributor.authorWarnatz, Klaus-
dc.contributor.authorHolland, Steven M.-
dc.contributor.authorUzel, Gülbü-
dc.contributor.authorCasanova, Jean-Laurent-
dc.contributor.authorTangye, Stuart G.-
dc.date.accessioned2022-09-27T06:04:43Z-
dc.date.available2022-09-27T06:04:43Z-
dc.date.issued2016-07-25-
dc.identifier.citationMa, C. S. vd. (2016). "Unique and shared signaling pathways cooperate to regulate the differentiation of human CD4(+) T cells into distinct effector subsets". Journal of Experimental Medicine, 213(8), 1589-1608.en_US
dc.identifier.issn0022-1007-
dc.identifier.issn1540-9538-
dc.identifier.urihttps://doi.org/10.1084/jem.20151467-
dc.identifier.urihttps://rupress.org/jem/article/213/8/1589/42083/Unique-and-shared-signaling-pathways-cooperate-to-
dc.identifier.urihttp://hdl.handle.net/11452/28838-
dc.description.abstractNaive CD4(+) T cells differentiate into specific effector subsets-Th1, Th2, Th17, and T follicular helper (Tfh)-that provide immunity against pathogen infection. The signaling pathways involved in generating these effector cells are partially known. However, the effects of mutations underlying human primary immunodeficiencies on these processes, and how they compromise specific immune responses, remain unresolved. By studying individuals with mutations in key signaling pathways, we identified nonredundant pathways regulating human CD4(+) T cell differentiation in vitro. IL12R beta 1/TYK2 and IFN-gamma R/STAT1 function in a feed-forward loop to induce Th1 cells, whereas IL-21/IL-21R/STAT3 signaling is required for Th17, Tfh, and IL-10-secreting cells. IL12R beta 1/TYK2 and NEMO are also required for Th17 induction. Strikingly, gain-of-function STAT1 mutations recapitulated the impact of dominant-negative STAT3 mutations on Tfh and Th17 cells, revealing a putative inhibitory effect of hypermorphic STAT1 over STAT3. These findings provide mechanistic insight into the requirements for human T cell effector function, and explain clinical manifestations of these immunodeficient conditions. Furthermore, they identify molecules that could be targeted to modulate CD4(+) T cell effector function in the settings of infection, vaccination, or immune dysregulation.en_US
dc.description.sponsorshipNational Health and Medical Research Council (NHMRC) of Australia - 596813en_US
dc.description.sponsorshipFederal Ministry of Education & Research (BMBF) - 01EO1303en_US
dc.description.sponsorshipRockefeller University Center for 541 Clinical and Translational science - 5UL1RR024143en_US
dc.description.sponsorshipNHMRC of Australia - 1042925en_US
dc.description.sponsorshipFulbright Commission 1008820en_US
dc.description.sponsorshipNHMRC of Australia - 1016953en_US
dc.description.sponsorshipUnited States Department of Health & Human Servicesen_US
dc.description.sponsorshipNational Institutes of Health (NIH) - USA - UL1RR024143en_US
dc.description.sponsorshipNIH National Center for Research Resources (NCRR)en_US
dc.description.sponsorshipThe Sir Jules Thorn Charitable Trust - 12JTAen_US
dc.description.sponsorshipNHMRC of Australia - 1066694en_US
dc.description.sponsorshipNHMRC of Australia - 1027400en_US
dc.description.sponsorshipNHMRC of Australia - 1004632en_US
dc.language.isoenen_US
dc.publisherRockefeller University Pressen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.rightsAtıf Gayri Ticari Türetilemez 4.0 Uluslararasıtr_TR
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectHyper-ige syndromeen_US
dc.subjectChronic mucocutaneous candidiasisen_US
dc.subjectFollicular-helper-cellsen_US
dc.subjectCommon variable immunodeficiencyen_US
dc.subjectEssential modulator mutationen_US
dc.subjectAntibody-responsesen_US
dc.subjectEctodermal dysplasiaen_US
dc.subjectIL-10 productionen_US
dc.subjectIcos deficiencyen_US
dc.subjectBCL6 expressionen_US
dc.subject.meshAntigens, differentiationen_US
dc.subject.meshCell differentiationen_US
dc.subject.meshFemaleen_US
dc.subject.meshHumansen_US
dc.subject.meshInterleukin-10en_US
dc.subject.meshMaleen_US
dc.subject.meshMutationen_US
dc.subject.meshSTAT1 transcription factoren_US
dc.subject.meshSTAT3 transcription factoren_US
dc.subject.meshTh1 cellsen_US
dc.subject.meshTh17 cellsen_US
dc.subject.meshTh2 cellsen_US
dc.titleUnique and shared signaling pathways cooperate to regulate the differentiation of human CD4(+) T cells into distinct effector subsetsen_US
dc.typeArticleen_US
dc.identifier.wos000380851200015tr_TR
dc.identifier.scopus2-s2.0-84982938276tr_TR
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergitr_TR
dc.contributor.departmentUludağ Üniversitesi/Tıp Fakültesi/Çocuk Sağlığı ve Hastalıkları Anabilim Dalı.tr_TR
dc.identifier.startpage1589tr_TR
dc.identifier.endpage1608tr_TR
dc.identifier.volume213tr_TR
dc.identifier.issue8tr_TR
dc.relation.journalJournal of Experimental Medicineen_US
dc.contributor.buuauthorKılıç, Sara Şebnem-
dc.contributor.researcheridAAH-1658-2021tr_TR
dc.relation.collaborationYurt içitr_TR
dc.relation.collaborationYurt dışıtr_TR
dc.relation.collaborationSanayitr_TR
dc.identifier.pubmed27401342tr_TR
dc.subject.wosImmunologyen_US
dc.subject.wosMedicine, research & experimentalen_US
dc.indexed.wosSCIEen_US
dc.indexed.scopusScopusen_US
dc.indexed.pubmedPubMeden_US
dc.wos.quartileQ1en_US
dc.contributor.scopusid34975059200tr_TR
dc.subject.scopusHelper Cell; Germinal Center; Tfh Cellen_US
dc.subject.emtreeCD4 antigenen_US
dc.subject.emtreeGamma interferonen_US
dc.subject.emtreeGamma interferon receptoren_US
dc.subject.emtreeL kappa B kinase gammaen_US
dc.subject.emtreeInterleukin 10en_US
dc.subject.emtreeInterleukin 12 receptor beta1en_US
dc.subject.emtreeInterleukin 21en_US
dc.subject.emtreeInterleukin 21 receptoren_US
dc.subject.emtreeProtein kinase TYK2en_US
dc.subject.emtreeSTAT1 proteinen_US
dc.subject.emtreeSTAT3 proteinen_US
dc.subject.emtreeSTAT4 proteinen_US
dc.subject.emtreeSTAT6 proteinen_US
dc.subject.emtreeDifferentiation antigenen_US
dc.subject.emtreeIL10 protein, mouseen_US
dc.subject.emtreeInterleukin 10en_US
dc.subject.emtreeSTAT1 protein, humanen_US
dc.subject.emtreeHumanen_US
dc.subject.emtreeArticleen_US
dc.subject.emtreeCD4+ T lymphocyteen_US
dc.subject.emtreeCell subpopulationen_US
dc.subject.emtreeControlled studyen_US
dc.subject.emtreeCytokine releaseen_US
dc.subject.emtreeEffector cellen_US
dc.subject.emtreeGain of function mutationen_US
dc.subject.emtreeGeneen_US
dc.subject.emtreeHumanen_US
dc.subject.emtreeHuman cellen_US
dc.subject.emtreeHumoral immunityen_US
dc.subject.emtreeImmune deficiencyen_US
dc.subject.emtreeImmunomodulationen_US
dc.subject.emtreeImmunoregulationen_US
dc.subject.emtreeIn vitro studyen_US
dc.subject.emtreeInfection sensitivityen_US
dc.subject.emtreeIntracellular signalingen_US
dc.subject.emtreeLymphocyte differentiationen_US
dc.subject.emtreePriority journalen_US
dc.subject.emtreeProtein phosphorylationen_US
dc.subject.emtreeSTAT1 geneen_US
dc.subject.emtreeSTAT3 geneen_US
dc.subject.emtreeTh0 cellen_US
dc.subject.emtreeTh1 cellen_US
dc.subject.emtreeTh17 cellen_US
dc.subject.emtreeTh2 cellen_US
dc.subject.emtreeCell differentiationen_US
dc.subject.emtreeCytologyen_US
dc.subject.emtreeFemaleen_US
dc.subject.emtreeGeneticsen_US
dc.subject.emtreeImmunologyen_US
dc.subject.emtreeMaleen_US
dc.subject.emtreeMutationen_US
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