{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T23:13:09Z","timestamp":1780614789761,"version":"3.54.1"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2012,11,1]],"date-time":"2012-11-01T00:00:00Z","timestamp":1351728000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>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-\u03baB 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-\u03baB pathway. Furthermore, the amount of Foxp3+ 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.<\/jats:p>","DOI":"10.4049\/jimmunol.1201993","type":"journal-article","created":{"date-parts":[[2012,10,13]],"date-time":"2012-10-13T08:55:18Z","timestamp":1350118518000},"page":"4770-4776","source":"Crossref","is-referenced-by-count":36,"title":["The Tumor Suppressor CYLD Controls the Function of Murine Regulatory T Cells"],"prefix":"10.1093","volume":"189","author":[{"given":"Sonja","family":"Reissig","sequence":"first","affiliation":[{"name":"Institute for Molecular Medicine, Johannes Gutenberg-University of Mainz , 55131 Mainz,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"H\u00f6velmeyer","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine, Johannes Gutenberg-University of Mainz , 55131 Mainz,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benno","family":"Weigmann","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine, Johannes Gutenberg-University of Mainz , 55131 Mainz,","place":["Germany"]},{"name":"Department of Internal Medicine I, University Hospital Erlangen, University Erlangen-N\u00fcrnberg , 91052 Erlangen,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexei","family":"Nikolaev","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine, Johannes Gutenberg-University of Mainz , 55131 Mainz,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bettina","family":"Kalt","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine, Johannes Gutenberg-University of Mainz , 55131 Mainz,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas F","family":"Wunderlich","sequence":"additional","affiliation":[{"name":"Department of Mouse Genetics and Metabolism, Institute for Genetics, University of Cologne , 50674 Cologne,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Hahn","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine, Johannes Gutenberg-University of Mainz , 55131 Mainz,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus F","family":"Neurath","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine, Johannes Gutenberg-University of Mainz , 55131 Mainz,","place":["Germany"]},{"name":"Department of Internal Medicine I, University Hospital Erlangen, University Erlangen-N\u00fcrnberg , 91052 Erlangen,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ari","family":"Waisman","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine, Johannes Gutenberg-University of Mainz , 55131 Mainz,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,11,15]]},"reference":[{"key":"2025032409361325900_r1","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/j.coph.2004.05.001","article-title":"Regulatory T cells","volume":"4","author":"Thompson","year":"2004","journal-title":"Curr. 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