Universität zu Köln

Reissig, Sonja, Hoevelmeyer, Nadine, Weigmann, Benno, Nikolaev, Alexei, Kalt, Bettina, Wunderlich, Thomas F., Hahn, Matthias, Neurath, Marcus F. and Waisman, Ari ORCID: 0000-0003-4304-8234 (2012). The Tumor Suppressor CYLD Controls the Function of Murine Regulatory T Cells. J. Immunol., 189 (10). S. 4770 - 4777. BETHESDA: AMER ASSOC IMMUNOLOGISTS. ISSN 0022-1767

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Abstract

CYLD was originally identified as a tumor suppressor gene mutated in familial cylindromatosis, an autosomal dominant predisposition to multiple benign neoplasms of the skin known as cylindromas. The CYLD protein is a deubiquitinating enzyme that acts as a negative regulator of NF-kappa B and JNK signaling through its interaction with NEMO and TNFR-associated factor 2. We have previously described a novel mouse strain that expresses solely and excessively a naturally occurring splice variant of CYLD (CYLDex7/8). In this study, we demonstrate that CYLD plays a critical role in Treg development and function. T cells of CYLDex7/8 mice had a hyperactive phenotype manifested by increased production of inflammatory cytokines and constitutive activation of the NF-kB pathway. Furthermore, the amount of Foxp(3+) regulatory T cells in these mice was markedly enhanced in thymus and peripheral organs. Importantly, these regulatory T cells displayed decreased expression levels of CD25 and CTLA-4 associated with impaired suppressive capacity. Hence, our data emphasize an essential role of CYLD in maintaining T cell homeostasis as well as normal T regulatory cell function, thereby controlling abnormal T cell responses. The Journal of Immunology, 2012, 189: 4770-4776.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Reissig, Sonja UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoevelmeyer, Nadine UNSPECIFIED UNSPECIFIED UNSPECIFIED Weigmann, Benno UNSPECIFIED UNSPECIFIED UNSPECIFIED Nikolaev, Alexei UNSPECIFIED UNSPECIFIED UNSPECIFIED Kalt, Bettina UNSPECIFIED UNSPECIFIED UNSPECIFIED Wunderlich, Thomas F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hahn, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Neurath, Marcus F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Waisman, Ari UNSPECIFIED orcid.org/0000-0003-4304-8234 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-478949
DOI:	10.4049/jimmunol.1201993
Journal or Publication Title:	J. Immunol.
Volume:	189
Number:	10
Page Range:	S. 4770 - 4777
Date:	2012
Publisher:	AMER ASSOC IMMUNOLOGISTS
Place of Publication:	BETHESDA
ISSN:	0022-1767
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language NF-KAPPA-B; DEUBIQUITINATING ENZYME CYLD; TRANSCRIPTION FACTOR; TGF-BETA; C-REL; FOXP3; CTLA-4; MAINTENANCE; HOMEOSTASIS; EXPRESSION Multiple languages Immunology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/47894