{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T13:58:01Z","timestamp":1779890281684,"version":"3.53.1"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2015,6,1]],"date-time":"2015-06-01T00:00:00Z","timestamp":1433116800000},"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":[[2015,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>IFN-\u03b2 is widely used in the treatment of multiple sclerosis, yet the mechanism facilitating its efficacy remains unclear. IL-2 production by activated T cells, including those mediating autoimmunity, and subsequent autocrine stimulation is vital for T cell expansion and function. In this study, we demonstrate that in mouse and human T cells, IFN-\u03b2 specifically inhibits the production of IL-2 upon TCR engagement without affecting other cytokines or activation markers. Rather than disrupting TCR signaling, IFN-\u03b2 alters histone modifications in the IL-2 promoter to retain the locus in an inaccessible configuration. This in turn is mediated through the upregulation of the transcriptional suppressor CREM by IFN-\u03b2 and consequent recruitment of histone deacetylases to the IL-2 promoter. In accordance, ablation of CREM expression or inhibition of histone deacetylases activity eliminates the suppressive effects of IFN-\u03b2 on IL-2 production. Collectively, these findings provide a molecular basis by which IFN-\u03b2 limits T cell responses.<\/jats:p>","DOI":"10.4049\/jimmunol.1403181","type":"journal-article","created":{"date-parts":[[2015,4,18]],"date-time":"2015-04-18T02:21:39Z","timestamp":1429323699000},"page":"5120-5128","source":"Crossref","is-referenced-by-count":14,"title":["IFN-\u03b2 Selectively Inhibits IL-2 Production through CREM-Mediated Chromatin Remodeling"],"prefix":"10.1093","volume":"194","author":[{"given":"Dennis C","family":"Otero","sequence":"first","affiliation":[{"name":"Division of Biological Sciences, University of California San Diego , La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy J","family":"Fares-Frederickson","sequence":"additional","affiliation":[{"name":"Division of Biological Sciences, University of California San Diego , La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menghong","family":"Xiao","sequence":"additional","affiliation":[{"name":"Division of Biological Sciences, University of California San Diego , La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren P","family":"Baker","sequence":"additional","affiliation":[{"name":"Biogen Idec , Cambridge, MA 02142"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"David","sequence":"additional","affiliation":[{"name":"Division of Biological Sciences, University of California San Diego , La Jolla, CA 92093"},{"name":"UC San Diego Moores Cancer Center, University of California San Diego , La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,6,1]]},"reference":[{"key":"2025030706370330100_r1","doi-asserted-by":"crossref","first-page":"491","DOI":"10.2165\/11591110-000000000-00000","article-title":"The mechanism of action of interferon-\u03b2 in relapsing multiple sclerosis","volume":"25","author":"Kieseier","year":"2011","journal-title":"CNS Drugs"},{"key":"2025030706370330100_r2","doi-asserted-by":"crossref","first-page":"e24972","DOI":"10.1371\/journal.pone.0024972","article-title":"T cell-intrinsic and -extrinsic contributions of the IFNAR\/STAT1-axis to thymocyte survival","volume":"6","author":"Moro","year":"2011","journal-title":"PLoS ONE"},{"key":"2025030706370330100_r3","doi-asserted-by":"crossref","first-page":"3289","DOI":"10.4049\/jimmunol.1203086","article-title":"IRF7-dependent IFN-\u03b2 production in response to RANKL promotes medullary thymic epithelial cell development","volume":"190","author":"Otero","year":"2013","journal-title":"J. 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