Reissig, Sonja, Tang, Yilang, Nikolaev, Alexei, Gerlach, Katharina, Wolf, Christine, Davari, Kathrin, Gallus, Christian, Masri, Joumana, Mufazalov, Ilgiz A., Neurath, Markus F., Wunderlich, F. Thomas, Schattenberg, Joern M., Galle, Peter R., Weigmann, Benno, Waisman, Ari, Glasmacher, Elke and Hoevelmeyer, Nadine (2017). Elevated levels of Bcl-3 inhibits Treg development and function resulting in spontaneous colitis. Nat. Commun., 8. LONDON: NATURE PUBLISHING GROUP. ISSN 2041-1723

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Abstract

Bcl-3 is an atypical NF-kappa B family member that regulates NF-kappa B-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 gamma delta T cells, but not alpha beta T cells. In Treg cells, Bcl-3 associates directly with NF-kappa B p50 to inhibit DNA binding of p50/p50 and p50/p65 NF-kappa B dimers, thereby regulating NF-kappa B-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-kappa B activity in Tregs to prevent colitis.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Reissig, SonjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tang, YilangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nikolaev, AlexeiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gerlach, KatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wolf, ChristineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Davari, KathrinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gallus, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Masri, JoumanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mufazalov, Ilgiz A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Neurath, Markus F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wunderlich, F. ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schattenberg, Joern M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Galle, Peter R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weigmann, BennoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Waisman, AriUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Glasmacher, ElkeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoevelmeyer, NadineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-233643
DOI: 10.1038/ncomms15069
Journal or Publication Title: Nat. Commun.
Volume: 8
Date: 2017
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 2041-1723
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
NF-KAPPA-B; INFLAMMATORY-BOWEL-DISEASE; REGULATORY T-CELLS; CHRONIC INTESTINAL INFLAMMATION; FOXP3 TRANSCRIPTION FACTOR; ONCOPROTEIN BCL-3; CROHNS-DISEASE; TARGETED DISRUPTION; ULCERATIVE-COLITIS; P50 HOMODIMERSMultiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/23364

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