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

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RESEARCH PRODUCT

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

Nadine Hövelmeyer Elke Glasmacher F. Thomas Wunderlich Christian Gallus Markus F. Neurath Jörn M. Schattenberg Kathrin Davari Alexei Nikolaev Katharina Gerlach Sonja Reißig Ari Waisman Yilang Tang Christine Wolf Joumana Masri Peter R. Galle Benno Weigmann Ilgiz A. Mufazalov

subject

Adult Male 0301 basic medicine P50 Science General Physics and Astronomy Biology T-Lymphocytes Regulatory Inflammatory bowel disease Article General Biochemistry Genetics and Molecular Biology Young Adult 03 medical and health sciences 0302 clinical medicine Immune system B-Cell Lymphoma 3 Protein Proto-Oncogene Proteins Gene expression medicine Animals Humans Colitis Mice Knockout Regulation of gene expression Multidisciplinary Effector HEK 293 cells Q NF-kappa B Transcription Factor RelA NF-kappa B p50 Subunit General Chemistry Middle Aged Colitis medicine.disease Mice Inbred C57BL HEK293 Cells 030104 developmental biology Gene Expression Regulation 030220 oncology & carcinogenesis Immunology Female Protein Binding Transcription Factors

description

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.

year	journal	country	edition	language
2017-04-01	Nature Communications

10.1038/ncomms15069 https://doaj.org/article/87d328bf46c940f9b17786b9c4f283ce