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IκB(NS) protein mediates regulatory T cell development via induction of the Foxp3 transcription factor.
- Source :
-
Immunity [Immunity] 2012 Dec 14; Vol. 37 (6), pp. 998-1008. Date of Electronic Publication: 2012 Nov 29. - Publication Year :
- 2012
-
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.<br /> (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Subjects :
- Adoptive Transfer
Animals
Apoptosis
Cell Differentiation immunology
Forkhead Transcription Factors genetics
Gene Expression Regulation
I-kappa B Proteins deficiency
I-kappa B Proteins genetics
Immunomodulation
Intracellular Signaling Peptides and Proteins
Lymphocyte Activation immunology
Male
Mice
Mice, Transgenic
NF-kappa B p50 Subunit metabolism
Promoter Regions, Genetic
Protein Binding
Proto-Oncogene Proteins c-rel metabolism
T-Lymphocytes, Regulatory drug effects
Transforming Growth Factor beta pharmacology
Forkhead Transcription Factors metabolism
I-kappa B Proteins metabolism
Proteins metabolism
T-Lymphocytes, Regulatory immunology
T-Lymphocytes, Regulatory metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4180
- Volume :
- 37
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Immunity
- Publication Type :
- Academic Journal
- Accession number :
- 23200824
- Full Text :
- https://doi.org/10.1016/j.immuni.2012.08.023