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http://purl.uniprot.org/citations/21677778http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/21677778http://www.w3.org/2000/01/rdf-schema#comment"

Background

Although in vitro IL-4 directs CD4 T cells to produce T helper 2 (Th2)-cytokines, these cytokines can be induced in vivo in the absence of IL-4-signalling. Thus, mechanism(s), different from the in vitro pathway for Th2-induction, contribute to in vivo Th2-differentiation. The pathway for in vivo IL-4-independent Th2-differentiation has yet to be characterized.

Findings

Helios (ikzf2), a member of the Ikaros transcription regulator family, is expressed in thymocytes and some antigen-matured T cells as well as in regulatory T cells. It has been proposed that Helios is a specific marker for thymus-derived regulatory T cells. Here, we show that mouse ovalbumin-specific CD4 (OTII) cells responding to alum-precipitated ovalbumin (alumOVA) upregulate Th2 features - GATA-3 and IL-4 - as well as Helios mRNA and protein. Helios is also upregulated in follicular helper T (TFh) cells in this response. By contrast, OTII cells responding to the Th1 antigen - live attenuated ovalbumin-expressing Salmonella - upregulate Th1 features - T-bet and IFN-γ - but not Helios. In addition, CD4 T cells induced to produce Th2 cytokines in vitro do not express Helios. The kinetics of Helios mRNA and protein induction mirrors that of GATA-3. The induction of IL-4, IL-13 and CXCR5 by alumOVA requires NF-κB1 and this is also needed for Helios upregulation. Importantly, Helios is induced in Th2 and TFh cells without parallel upregulation of Foxp3. These findings suggested a key role for Helios in Th2 and TFh development in response to alum-protein vaccines. We tested this possibility using Helios-deficient OTII cells and found this deficiency had no discernable impact on Th2 and TFh differentiation in response to alumOVA.

Conclusions

Helios is selectively upregulated in CD4 T cells during Th2 and TFh responses to alum-protein vaccines in vivo, but the functional significance of this upregulation remains uncertain."xsd:string
http://purl.uniprot.org/citations/21677778http://purl.org/dc/terms/identifier"doi:10.1371/journal.pone.0020731"xsd:string
http://purl.uniprot.org/citations/21677778http://purl.uniprot.org/core/author"Cunningham A.F."xsd:string
http://purl.uniprot.org/citations/21677778http://purl.uniprot.org/core/author"Chan S."xsd:string
http://purl.uniprot.org/citations/21677778http://purl.uniprot.org/core/author"Bobat S."xsd:string
http://purl.uniprot.org/citations/21677778http://purl.uniprot.org/core/author"Mohr E."xsd:string
http://purl.uniprot.org/citations/21677778http://purl.uniprot.org/core/author"Kastner P."xsd:string
http://purl.uniprot.org/citations/21677778http://purl.uniprot.org/core/author"Benezech C."xsd:string
http://purl.uniprot.org/citations/21677778http://purl.uniprot.org/core/author"Toellner K.M."xsd:string
http://purl.uniprot.org/citations/21677778http://purl.uniprot.org/core/author"Serre K."xsd:string
http://purl.uniprot.org/citations/21677778http://purl.uniprot.org/core/author"Maclennan I.C."xsd:string
http://purl.uniprot.org/citations/21677778http://purl.uniprot.org/core/author"Bird R."xsd:string
http://purl.uniprot.org/citations/21677778http://purl.uniprot.org/core/author"Desanti G."xsd:string
http://purl.uniprot.org/citations/21677778http://purl.uniprot.org/core/date"2011"xsd:gYear
http://purl.uniprot.org/citations/21677778http://purl.uniprot.org/core/name"PLoS One"xsd:string
http://purl.uniprot.org/citations/21677778http://purl.uniprot.org/core/pages"e20731"xsd:string
http://purl.uniprot.org/citations/21677778http://purl.uniprot.org/core/title"Helios is associated with CD4 T cells differentiating to T helper 2 and follicular helper T cells in vivo independently of Foxp3 expression."xsd:string
http://purl.uniprot.org/citations/21677778http://purl.uniprot.org/core/volume"6"xsd:string
http://purl.uniprot.org/citations/21677778http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/21677778
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