IκB(NS) Protein Mediates Regulatory T Cell Development via Induction of the Foxp3 Transcription Factor.

2.50
Hdl Handle:
http://hdl.handle.net/10033/267692
Title:
IκB(NS) Protein Mediates Regulatory T Cell Development via Induction of the Foxp3 Transcription Factor.
Authors:
Schuster, Marc; Glauben, Rainer; Plaza-Sirvent, Carlos; Schreiber, Lisa; Annemann, Michaela; Floess, Stefan; Kühl, Anja A; Clayton, Linda K; Sparwasser, Tim ( 0000-0001-5645-902X ) ; Schulze-Osthoff, Klaus; Pfeffer, Klaus; Huehn, Jochen; Siegmund, Britta; Schmitz, Ingo ( 0000-0002-5360-0419 )
Abstract:
Forkhead box P3 positive (Foxp3(+)) regulatory T (Treg) cells suppress immune responses and regulate peripheral tolerance. Here we show that the atypical inhibitor of NFκB (IκB) IκB(NS) drives Foxp3 expression via association with the promoter and the conserved noncoding sequence 3 (CNS3) of the Foxp3 locus. Consequently, IκB(NS) deficiency leads to a substantial reduction of Foxp3(+) Treg cells in vivo and impaired Foxp3 induction upon transforming growth factor-β (TGF-β) treatment in vitro. Moreover, fewer Foxp3(+) Treg cells developed from IκB(NS)-deficient CD25(-)CD4(+) T cells adoptively transferred into immunodeficient recipients. Importantly, IκB(NS) was required for the transition of immature GITR(+)CD25(+)Foxp3(-) thymic Treg cell precursors into Foxp3(+) cells. In contrast to mice lacking c-Rel or Carma1, IκB(NS)-deficient mice do not show reduced Treg precursor cells. Our results demonstrate that IκB(NS) critically regulates Treg cell development in the thymus and during gut inflammation, indicating that strategies targeting IκB(NS) could modulate the Treg cell compartment.
Affiliation:
Systems-oriented Immunology and Inflammation Research, Helmholtz Center for Infection Research, 38124 Braunschweig, Germany, and Institute for Molecular and Clinical Immunology, Otto-von-Guericke University, 39120 Magdeburg, Germany.
Citation:
IκB(NS) Protein Mediates Regulatory T Cell Development via Induction of the Foxp3 Transcription Factor. 2012, 37 (6):998-1008 Immunity
Journal:
Immunity
Issue Date:
14-Dec-2012
URI:
http://hdl.handle.net/10033/267692
DOI:
10.1016/j.immuni.2012.08.023
PubMed ID:
23200824
Type:
Article
Language:
en
ISSN:
1097-4180
Appears in Collections:
publications of the TwinCore unit Infection immunology

Full metadata record

DC FieldValue Language
dc.contributor.authorSchuster, Marcen_GB
dc.contributor.authorGlauben, Raineren_GB
dc.contributor.authorPlaza-Sirvent, Carlosen_GB
dc.contributor.authorSchreiber, Lisaen_GB
dc.contributor.authorAnnemann, Michaelaen_GB
dc.contributor.authorFloess, Stefanen_GB
dc.contributor.authorKühl, Anja Aen_GB
dc.contributor.authorClayton, Linda Ken_GB
dc.contributor.authorSparwasser, Timen_GB
dc.contributor.authorSchulze-Osthoff, Klausen_GB
dc.contributor.authorPfeffer, Klausen_GB
dc.contributor.authorHuehn, Jochenen_GB
dc.contributor.authorSiegmund, Brittaen_GB
dc.contributor.authorSchmitz, Ingoen_GB
dc.date.accessioned2013-01-30T14:02:36Zen
dc.date.available2013-01-30T14:02:36Zen
dc.date.issued2012-12-14en
dc.identifier.citationIκB(NS) Protein Mediates Regulatory T Cell Development via Induction of the Foxp3 Transcription Factor. 2012, 37 (6):998-1008 Immunityen_GB
dc.identifier.issn1097-4180en
dc.identifier.pmid23200824en
dc.identifier.doi10.1016/j.immuni.2012.08.023en
dc.identifier.urihttp://hdl.handle.net/10033/267692en
dc.description.abstractForkhead box P3 positive (Foxp3(+)) regulatory T (Treg) cells suppress immune responses and regulate peripheral tolerance. Here we show that the atypical inhibitor of NFκB (IκB) IκB(NS) drives Foxp3 expression via association with the promoter and the conserved noncoding sequence 3 (CNS3) of the Foxp3 locus. Consequently, IκB(NS) deficiency leads to a substantial reduction of Foxp3(+) Treg cells in vivo and impaired Foxp3 induction upon transforming growth factor-β (TGF-β) treatment in vitro. Moreover, fewer Foxp3(+) Treg cells developed from IκB(NS)-deficient CD25(-)CD4(+) T cells adoptively transferred into immunodeficient recipients. Importantly, IκB(NS) was required for the transition of immature GITR(+)CD25(+)Foxp3(-) thymic Treg cell precursors into Foxp3(+) cells. In contrast to mice lacking c-Rel or Carma1, IκB(NS)-deficient mice do not show reduced Treg precursor cells. Our results demonstrate that IκB(NS) critically regulates Treg cell development in the thymus and during gut inflammation, indicating that strategies targeting IκB(NS) could modulate the Treg cell compartment.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to Immunityen_GB
dc.titleIκB(NS) Protein Mediates Regulatory T Cell Development via Induction of the Foxp3 Transcription Factor.en
dc.typeArticleen
dc.contributor.departmentSystems-oriented Immunology and Inflammation Research, Helmholtz Center for Infection Research, 38124 Braunschweig, Germany, and Institute for Molecular and Clinical Immunology, Otto-von-Guericke University, 39120 Magdeburg, Germany.en_GB
dc.identifier.journalImmunityen_GB

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