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We previously identified the tumor suppressor gene transformed follicular lymphoma (TFL) on 6q25 in a patient with follicular lymphoma, which transformed into diffuse large B cell lymphoma. TFL families have a common RNase domain that governs macrophage-mediated inflammation. In human peripheral blood, TFL is dominantly expressed at the glycine- and tryptophan-rich cytoplasmic processing bodies of T lymphocytes, and it is persistently upregulated in activated T cells. To address its physiological role, we established TFL\u2212\/\u2212 mice in which TFL\u2212\/\u2212 lymphocytes proliferated more rapidly than TFL+\/+ upon stimulation with inappropriate cytokine secretion, including IL-2, IL-6, and IL-10. Moreover, TFL inhibited the synthesis of cytokines such as IL-2, IL-6, IL-10, TNF-\u03b1, and IL-17a by 3\u2032 untranslated region RNA degradation. Experimental autoimmune encephalitis induced in TFL\u2212\/\u2212 mice demonstrated persistent severe paralysis. CNS-infiltrated CD4+ T cells in TFL\u2212\/\u2212 mice contained a higher proportion of Th17 cells than did those in TFL+\/+ mice during the resolution phase, and IL-17a mRNA levels were markedly increased in TFL\u2212\/\u2212 cells. These results suggest that TFL may play an important role in attenuating local inflammation by suppressing the infiltration of Th17 cells in the CNS during the resolution phase of experimental autoimmune encephalitis. TFL is a novel gradual and persistent posttranscriptional regulator, and the TFL-driven attenuation of excessive inflammation could contribute to recovery from T cell\u2013mediated autoimmune diseases.<\/jats:p>","DOI":"10.4049\/jimmunol.1301619","type":"journal-article","created":{"date-parts":[[2014,1,11]],"date-time":"2014-01-11T04:11:33Z","timestamp":1389413493000},"page":"1512-1524","source":"Crossref","is-referenced-by-count":42,"title":["Posttranscriptional Modulation of Cytokine Production in T Cells for the Regulation of Excessive Inflammation by TFL"],"prefix":"10.1093","volume":"192","author":[{"given":"Kentaro","family":"Minagawa","sequence":"first","affiliation":[{"name":"Division of Hematology, Department of Medicine, Kobe University Graduate School of Medicine , Kobe 650-0017,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanako","family":"Wakahashi","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Medicine, Kobe University Graduate School of Medicine , Kobe 650-0017,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Kawano","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Medicine, Kobe University Graduate School of Medicine , Kobe 650-0017,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichiro","family":"Nishikawa","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Medicine, Kobe University Graduate School of Medicine , Kobe 650-0017,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chie","family":"Fukui","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Medicine, Kobe University Graduate School of Medicine , Kobe 650-0017,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Kawano","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Medicine, Kobe University Graduate School of Medicine , Kobe 650-0017,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noboru","family":"Asada","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Medicine, Kobe University Graduate School of Medicine , Kobe 650-0017,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari","family":"Sato","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Medicine, Kobe University Graduate School of Medicine , Kobe 650-0017,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Sada","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Medicine, Kobe University Graduate School of Medicine , Kobe 650-0017,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshio","family":"Katayama","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Medicine, Kobe University Graduate School of Medicine , Kobe 650-0017,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshimitsu","family":"Matsui","sequence":"additional","affiliation":[{"name":"Department of Hematology, Nishiwaki Municipal Hospital , Nishiwaki 677-0043,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,2,15]]},"reference":[{"key":"2025032404123498000_r1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/nrm2080","article-title":"P bodies: at the crossroads of post-transcriptional pathways","volume":"8","author":"Eulalio","year":"2007","journal-title":"Nat. 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