Differentiating the roles of STAT5B and STAT5A in human CD4(+) T cells

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorJENKS, Jennifer A.
dc.contributor.authorSEKI, Scott
dc.contributor.authorKANAI, Takahiro
dc.contributor.authorHUANG, Jennifer
dc.contributor.authorMORGAN, Alexander A.
dc.contributor.authorSCALCO, Renata C.
dc.contributor.authorNATH, Ruhi
dc.contributor.authorBUCAYU, Robert
dc.contributor.authorWIT, Jan M.
dc.contributor.authorAL-HERZ, Waleed
dc.contributor.authorRAMADAN, Dina
dc.contributor.authorJORGE, Alexander A.
dc.contributor.authorBACCHETTA, Rosa
dc.contributor.authorHWA, Vivian
dc.contributor.authorROSENFELD, Ron
dc.contributor.authorNADEAU, Kari C.
dc.date.accessioned2014-01-28T22:17:19Z
dc.date.available2014-01-28T22:17:19Z
dc.date.issued2013
dc.description.abstractSTAT5A and STAT5B are highly homologous proteins whose distinctive roles in human immunity remain unclear. However, STAT5A sufficiency cannot compensate for STAT5B defects, and human STAT5B deficiency, a rare autosomal recessive primary immunodeficiency, is characterized by chronic lung disease, growth failure and autoimmunity associated with regulatory T cell (Treg) reduction. We therefore hypothesized that STAT5A and STAT5B play unique roles in CD4(+) T cells. Upon knocking down STAT5A or STAT5B in human primary T cells, we found differentially regulated expression of FOXP3 and IL-2R in STAT5B knockdown T cells and down-regulated Bcl-X only in STAT5A knockdown T cells. Functional ex vivo studies in homozygous STAT5B-deficient patients showed reduced FOXP3 expression with impaired regulatory function of STAT5B-null Treg cells, also of increased memory phenotype. These results indicate that STAT5B and STAT5A act partly as non-redundant transcription factors and that STAT5B is more critical for Treg maintenance and function in humans.
dc.description.indexMEDLINE
dc.description.sponsorshipClinical Immunological Society Junior Faculty Award
dc.identifier.citationCLINICAL IMMUNOLOGY, v.148, n.2, p.227-236, 2013
dc.identifier.doi10.1016/j.clim.2013.04.014
dc.identifier.issn1521-6616
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/3907
dc.language.isoeng
dc.publisherACADEMIC PRESS INC ELSEVIER SCIENCE
dc.relation.ispartofClinical Immunology
dc.rightsrestrictedAccess
dc.rights.holderCopyright ACADEMIC PRESS INC ELSEVIER SCIENCE
dc.subjectSTAT5
dc.subjectRegulatory T cells (Treg)
dc.subjectT cell development
dc.subject.otherfoxp3 expression
dc.subject.otherdeficiency
dc.subject.othertolerance
dc.subject.othergene
dc.subject.otherimmunodeficiency
dc.subject.otherproteins
dc.subject.othermutation
dc.subject.otherdisease
dc.subject.wosImmunology
dc.titleDifferentiating the roles of STAT5B and STAT5A in human CD4(+) T cells
dc.typearticle
dc.type.categoryoriginal article
dc.type.versionpublishedVersion
dspace.entity.typePublication
hcfmusp.affiliation.countryHolanda
hcfmusp.affiliation.countryItália
hcfmusp.affiliation.countryEstados Unidos
hcfmusp.affiliation.countryKuwait
hcfmusp.affiliation.countryisous
hcfmusp.affiliation.countryisonl
hcfmusp.affiliation.countryisokw
hcfmusp.affiliation.countryisoit
hcfmusp.author.externalJENKS, Jennifer A.:Stanford Univ, Div Immunol & Allergy, Stanford, CA 94305 USA
hcfmusp.author.externalSEKI, Scott:Stanford Univ, Div Immunol & Allergy, Stanford, CA 94305 USA
hcfmusp.author.externalKANAI, Takahiro:Stanford Univ, Div Immunol & Allergy, Stanford, CA 94305 USA
hcfmusp.author.externalHUANG, Jennifer:Stanford Univ, Div Immunol & Allergy, Stanford, CA 94305 USA
hcfmusp.author.externalMORGAN, Alexander A.:Stanford Univ, Dept Biochem, Stanford, CA 94305 USA
hcfmusp.author.externalNATH, Ruhi:Stanford Univ, Div Immunol & Allergy, Stanford, CA 94305 USA
hcfmusp.author.externalBUCAYU, Robert:Stanford Univ, Div Immunol & Allergy, Stanford, CA 94305 USA
hcfmusp.author.externalWIT, Jan M.:Leiden Univ, Med Ctr, Dept Pediat, Leiden, Netherlands
hcfmusp.author.externalAL-HERZ, Waleed:Kuwait Univ, Fac Med, Dept Pediat, Safat 13060, Kuwait
hcfmusp.author.externalBACCHETTA, Rosa:Stanford Univ, Div Immunol & Allergy, Stanford, CA 94305 USA; Ist Sci San Raffaele, San Raffaele Telethon Inst Gene Therapy HSR TIGET, Div Regenerat Med Stem Cells & Gene Therapy, I-20132 Milan, Italy
hcfmusp.author.externalHWA, Vivian:Oregon Hlth & Sci Univ, Dept Pediat, Portland, OR 97239 USA
hcfmusp.author.externalROSENFELD, Ron:Oregon Hlth & Sci Univ, Dept Pediat, Portland, OR 97239 USA
hcfmusp.author.externalNADEAU, Kari C.:Stanford Univ, Div Immunol & Allergy, Stanford, CA 94305 USA
hcfmusp.citation.scopus40
hcfmusp.contributor.author-fmusphcRENATA DA CUNHA SCALCO
hcfmusp.contributor.author-fmusphcALEXANDER AUGUSTO DE LIMA JORGE
hcfmusp.description.beginpage227
hcfmusp.description.endpage236
hcfmusp.description.issue2
hcfmusp.description.volume148
hcfmusp.origemWOS
hcfmusp.origem.pubmed23773921
hcfmusp.origem.scopus2-s2.0-84879319122
hcfmusp.origem.wosWOS:000322101300009
hcfmusp.publisher.citySAN DIEGO
hcfmusp.publisher.countryUSA
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