IκB(NS) Protein Mediates Regulatory T Cell Development via Induction of the Foxp3 Transcription Factor.
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Authors
Schuster, MarcGlauben, Rainer
Plaza-Sirvent, Carlos
Schreiber, Lisa
Annemann, Michaela
Floess, Stefan
Kühl, Anja A
Clayton, Linda K
Sparwasser, Tim
Schulze-Osthoff, Klaus
Pfeffer, Klaus
Huehn, Jochen
Siegmund, Britta
Schmitz, Ingo
Issue Date
2012-12-14
Metadata
Show full item recordAbstract
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.Citation
IκB(NS) Protein Mediates Regulatory T Cell Development via Induction of the Foxp3 Transcription Factor. 2012, 37 (6):998-1008 ImmunityAffiliation
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.Journal
ImmunityPubMed ID
23200824Type
ArticleLanguage
enISSN
1097-4180ae974a485f413a2113503eed53cd6c53
10.1016/j.immuni.2012.08.023
Scopus Count
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