Regulatory T cells facilitate the nuclear accumulation of inducible cAMP early repressor (ICER) and suppress nuclear factor of activated T cell c1 (NFATc1).

2.50
Hdl Handle:
http://hdl.handle.net/10033/142844
Title:
Regulatory T cells facilitate the nuclear accumulation of inducible cAMP early repressor (ICER) and suppress nuclear factor of activated T cell c1 (NFATc1).
Authors:
Vaeth, Martin; Gogishvili, Tea; Bopp, Tobias; Klein, Matthias; Berberich-Siebelt, Friederike; Gattenloehner, Stefan; Avots, Andris; Sparwasser, Tim; Grebe, Nadine; Schmitt, Edgar; Hünig, Thomas; Serfling, Edgar; Bodor, Josef
Abstract:
Inducible cAMP early repressor (ICER) is a transcriptional repressor, which, because of alternate promoter use, is generated from the 3' region of the cAMP response modulator (Crem) gene. Its expression and nuclear occurrence are elevated by high cAMP levels in naturally occurring regulatory T cells (nTregs). Using two mouse models, we demonstrate that nTregs control the cellular localization of ICER/CREM, and thereby inhibit IL-2 synthesis in conventional CD4(+) T cells. Ablation of nTregs in depletion of regulatory T-cell (DEREG) mice resulted in cytosolic localization of ICER/CREM and increased IL-2 synthesis upon stimulation. Direct contacts between nTregs and conventional CD4(+) T cells led to nuclear accumulation of ICER/CREM and suppression of IL-2 synthesis on administration of CD28 superagonistic (CD28SA) Ab. In a similar way, nTregs communicated with B cells and induced the cAMP-driven nuclear localization of ICER/CREM. High levels of ICER suppressed the induction of nuclear factor of activated T cell c1 (Nfatc1) gene in T cells whose inducible Nfatc1 P1 promoter bears two highly conserved cAMP-responsive elements to which ICER/CREM can bind. These findings suggest that nTregs suppress T-cell responses by the cAMP-dependent nuclear accumulation of ICER/CREM and inhibition of NFATc1 and IL-2 induction.
Affiliation:
Department of Molecular Pathology, Institute of Pathology, University of Wurzburg, D-97080 Wurzburg, Germany.
Citation:
Regulatory T cells facilitate the nuclear accumulation of inducible cAMP early repressor (ICER) and suppress nuclear factor of activated T cell c1 (NFATc1). 2011, 108 (6):2480-5 Proc. Natl. Acad. Sci. U.S.A.
Journal:
Proceedings of the National Academy of Sciences of the United States of America
Issue Date:
8-Feb-2011
URI:
http://hdl.handle.net/10033/142844
DOI:
10.1073/pnas.1009463108
PubMed ID:
21262800
Type:
Article
Language:
en
ISSN:
1091-6490
Appears in Collections:
publications of the TwinCore unit Infection immunology

Full metadata record

DC FieldValue Language
dc.contributor.authorVaeth, Martinen
dc.contributor.authorGogishvili, Teaen
dc.contributor.authorBopp, Tobiasen
dc.contributor.authorKlein, Matthiasen
dc.contributor.authorBerberich-Siebelt, Friederikeen
dc.contributor.authorGattenloehner, Stefanen
dc.contributor.authorAvots, Andrisen
dc.contributor.authorSparwasser, Timen
dc.contributor.authorGrebe, Nadineen
dc.contributor.authorSchmitt, Edgaren
dc.contributor.authorHünig, Thomasen
dc.contributor.authorSerfling, Edgaren
dc.contributor.authorBodor, Josefen
dc.date.accessioned2011-09-21T14:08:19Z-
dc.date.available2011-09-21T14:08:19Z-
dc.date.issued2011-02-08-
dc.identifier.citationRegulatory T cells facilitate the nuclear accumulation of inducible cAMP early repressor (ICER) and suppress nuclear factor of activated T cell c1 (NFATc1). 2011, 108 (6):2480-5 Proc. Natl. Acad. Sci. U.S.A.en
dc.identifier.issn1091-6490-
dc.identifier.pmid21262800-
dc.identifier.doi10.1073/pnas.1009463108-
dc.identifier.urihttp://hdl.handle.net/10033/142844-
dc.description.abstractInducible cAMP early repressor (ICER) is a transcriptional repressor, which, because of alternate promoter use, is generated from the 3' region of the cAMP response modulator (Crem) gene. Its expression and nuclear occurrence are elevated by high cAMP levels in naturally occurring regulatory T cells (nTregs). Using two mouse models, we demonstrate that nTregs control the cellular localization of ICER/CREM, and thereby inhibit IL-2 synthesis in conventional CD4(+) T cells. Ablation of nTregs in depletion of regulatory T-cell (DEREG) mice resulted in cytosolic localization of ICER/CREM and increased IL-2 synthesis upon stimulation. Direct contacts between nTregs and conventional CD4(+) T cells led to nuclear accumulation of ICER/CREM and suppression of IL-2 synthesis on administration of CD28 superagonistic (CD28SA) Ab. In a similar way, nTregs communicated with B cells and induced the cAMP-driven nuclear localization of ICER/CREM. High levels of ICER suppressed the induction of nuclear factor of activated T cell c1 (Nfatc1) gene in T cells whose inducible Nfatc1 P1 promoter bears two highly conserved cAMP-responsive elements to which ICER/CREM can bind. These findings suggest that nTregs suppress T-cell responses by the cAMP-dependent nuclear accumulation of ICER/CREM and inhibition of NFATc1 and IL-2 induction.en
dc.language.isoenen
dc.subject.meshActive Transport, Cell Nucleusen
dc.subject.meshAnimalsen
dc.subject.meshAntibodiesen
dc.subject.meshAntigens, CD28en
dc.subject.meshCell Nucleusen
dc.subject.meshCyclic AMPen
dc.subject.meshCyclic AMP Response Element Modulatoren
dc.subject.meshInterleukin-2en
dc.subject.meshLymphocyte Activationen
dc.subject.meshMiceen
dc.subject.meshMice, Inbred BALB Cen
dc.subject.meshMice, Knockouten
dc.subject.meshNFATC Transcription Factorsen
dc.subject.meshResponse Elementsen
dc.subject.meshT-Lymphocytes, Regulatoryen
dc.titleRegulatory T cells facilitate the nuclear accumulation of inducible cAMP early repressor (ICER) and suppress nuclear factor of activated T cell c1 (NFATc1).en
dc.typeArticleen
dc.contributor.departmentDepartment of Molecular Pathology, Institute of Pathology, University of Wurzburg, D-97080 Wurzburg, Germany.en
dc.identifier.journalProceedings of the National Academy of Sciences of the United States of Americaen

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