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

Reissig S, Tang Y, Nikolaev A, Gerlach K, Wolf C, Davari K, Gallus C, Masri J, Mufazalov IA, Neurath M, Wunderlich FT, Schattenberg JM, Galle PR, Weigmann B, Waisman A, Glasmacher E, Hoevelmeyer N (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Nature Communications Nature Publishing Group: Nature Communications

Book Volume: 8

DOI: 10.1038/ncomms15069

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.

Authors with CRIS profile

Katharina Gerlach Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Markus Neurath Lehrstuhl für Innere Medizin I Benno Weigmann Medizinische Fakultät

Additional Organisation(s)

Interdisziplinäres Zentrum für Klinische Forschung

Involved external institutions

Johannes Gutenberg-Universität Mainz (JGU) DE Germany (DE) Deutsches Zentrum für Diabetesforschung e.V. (DZD) DE Germany (DE) Max-Planck-Institut für Stoffwechselforschung / Max Planck Institute for Metabolism Research DE Germany (DE)

How to cite

APA:

Reissig, S., Tang, Y., Nikolaev, A., Gerlach, K., Wolf, C., Davari, K.,... Hoevelmeyer, N. (2017). Elevated levels of Bcl-3 inhibits Treg development and function resulting in spontaneous colitis. Nature Communications, 8. https://doi.org/10.1038/ncomms15069

MLA:

Reissig, Sonja, et al. "Elevated levels of Bcl-3 inhibits Treg development and function resulting in spontaneous colitis." Nature Communications 8 (2017).

BibTeX: Download