Elevated levels of Bcl-3 inhibits Treg development and function resulting in spontaneous colitis

Sonja Reißig (), Yilang Tang, Alexei Nikolaev, Katharina Gerlach, Christine Wolf, Kathrin Davari, Christian Gallus, Joumana Masri, Ilgiz A. Mufazalov, Markus F. Neurath, F. Thomas Wunderlich, Jörn M. Schattenberg, Peter R. Galle, Benno Weigmann, Ari Waisman, Elke Glasmacher and Nadine Hövelmeyer ()
Additional contact information
Sonja Reißig: Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg, University of Mainz
Yilang Tang: Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg, University of Mainz
Alexei Nikolaev: Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg, University of Mainz
Katharina Gerlach: University Erlangen-Nürnberg
Christine Wolf: Helmholtz Zentrum München, Institute of Diabetes and Obesity (IDO), German Center for Diabetes Research (DZD)
Kathrin Davari: Helmholtz Zentrum München, Institute of Diabetes and Obesity (IDO), German Center for Diabetes Research (DZD)
Christian Gallus: Helmholtz Zentrum München, Institute of Diabetes and Obesity (IDO), German Center for Diabetes Research (DZD)
Joumana Masri: Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg, University of Mainz
Ilgiz A. Mufazalov: Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg, University of Mainz
Markus F. Neurath: University Erlangen-Nürnberg
F. Thomas Wunderlich: Max Planck Institute for Metabolism Research, CECAD, CMMC, Institute for Genetics
Jörn M. Schattenberg: University Medical Center of the Johannes Gutenberg, University of Mainz
Peter R. Galle: University Medical Center of the Johannes Gutenberg, University of Mainz
Benno Weigmann: University Erlangen-Nürnberg
Ari Waisman: Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg, University of Mainz
Elke Glasmacher: Helmholtz Zentrum München, Institute of Diabetes and Obesity (IDO), German Center for Diabetes Research (DZD)
Nadine Hövelmeyer: Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg, University of Mainz

Nature Communications, 2017, vol. 8, issue 1, 1-14

Abstract: Abstract Bcl-3 is an atypical NF-κB family member that regulates NF-κB-dependent gene expression in effector T cells, but a cell-intrinsic function in regulatory T (Treg) cells and colitis is not clear. Here we show that Bcl-3 expression levels in colonic T cells correlate with disease manifestation in patients with inflammatory bowel disease. Mice with T-cell-specific overexpression of Bcl-3 develop severe colitis that can be attributed to defective Treg cell development and function, leading to the infiltration of immune cells such as pro-inflammatory γδT cells, but not αβ T cells. In Treg cells, Bcl-3 associates directly with NF-κB p50 to inhibit DNA binding of p50/p50 and p50/p65 NF-κB dimers, thereby regulating NF-κB-mediated gene expression. This study thus reveals intrinsic functions of Bcl-3 in Treg cells, identifies Bcl-3 as a potential prognostic marker for colitis and illustrates the mechanism by which Bcl-3 regulates NF-κB activity in Tregs to prevent colitis.

Date: 2017
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms15069 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15069

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms15069

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().