{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:28:09Z","timestamp":1787030889359,"version":"build-2736575974"},"reference-count":59,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2018,3,1]],"date-time":"2018-03-01T00:00:00Z","timestamp":1519862400000},"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":[[2018,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>IL-10 is a pleiotropic cytokine with multifaceted functions in establishing immune homeostasis. Although expressed by Th1 and Th2 cells, conventional Th1 cells produce marginal levels of IL-10 compared with their Th2 counterparts. In this study, we investigated the epigenetic mechanisms of Il-10 gene expression in Th1 cells. Bioinformatics EMBOSS CpG plot analysis and bisulfite pyrosequencing revealed three CpG DNA methylation sites in the Il-10 gene locus. Progressive DNA methylation at all of the CpG regions of interest (ROIs) established a repressive program of Il-10 gene expression in Th1 cells. Interestingly, Th1 cells treated with IL-12 and IL-27 cytokines, thereby mimicking a chronic inflammatory condition in vivo, displayed a significant increase in IL-10 production that was accompanied by selective DNA demethylation at ROI 3 located in intron 3. IL-10\u2013producing T cells isolated from lymphocytic choriomeningitis virus\u2013infected mice also showed enhanced DNA demethylation at ROI 3. Binding of STAT1 and STAT3 to demethylated ROI 3 enhanced IL-10 expression in an IL-12\/IL-27\u2013dependent manner. Accordingly, CD4+ T cells isolated from STAT1- or STAT3-knockout mice were significantly defective in IL-10 production. Our data suggest that, although stably maintained DNA methylation at the promoter may repress IL-10 expression in Th1 cells, locus-specific reversible DNA demethylation may serve as a threshold platform to control transient Il-10 gene expression.<\/jats:p>","DOI":"10.4049\/jimmunol.1701162","type":"journal-article","created":{"date-parts":[[2018,1,26]],"date-time":"2018-01-26T10:50:10Z","timestamp":1516963810000},"page":"1865-1875","source":"Crossref","is-referenced-by-count":10,"title":["Locus-Specific Reversible DNA Methylation Regulates Transient IL-10 Expression in Th1 Cells"],"prefix":"10.1093","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5428-4158","authenticated-orcid":false,"given":"Won","family":"Hwang","sequence":"first","affiliation":[{"name":"Academy of Immunology and Microbiology, Institute for Basic Science , Pohang 37673,","place":["Republic of Korea"]},{"name":"School of Life Sciences, Gwangju Institute of Science and Technology , Gwangju 61005,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7977-0408","authenticated-orcid":false,"given":"Choong-Gu","family":"Lee","sequence":"additional","affiliation":[{"name":"Academy of Immunology and Microbiology, Institute for Basic Science , Pohang 37673,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changhon","family":"Lee","sequence":"additional","affiliation":[{"name":"Academy of Immunology and Microbiology, Institute for Basic Science , Pohang 37673,","place":["Republic of Korea"]},{"name":"Division of Integrative Bioscience and Biotechnology, Pohang University of Science and Technology , Pohang 37673,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravi","family":"Verma","sequence":"additional","affiliation":[{"name":"Academy of Immunology and Microbiology, Institute for Basic Science , Pohang 37673,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dipayan","family":"Rudra","sequence":"additional","affiliation":[{"name":"Academy of Immunology and Microbiology, Institute for Basic Science , Pohang 37673,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8184-5982","authenticated-orcid":false,"given":"Zee Yong","family":"Park","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Gwangju Institute of Science and Technology , Gwangju 61005,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3173-1856","authenticated-orcid":false,"given":"Sin-Hyeog","family":"Im","sequence":"additional","affiliation":[{"name":"Academy of Immunology and Microbiology, Institute for Basic Science , Pohang 37673,","place":["Republic of Korea"]},{"name":"Division of Integrative Bioscience and Biotechnology, Pohang University of Science and Technology , Pohang 37673,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,3,1]]},"reference":[{"key":"2025030610052553800_r1","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1111\/j.1600-065X.2008.00706.x","article-title":"Interleukin-10: new perspectives on an old cytokine","volume":"226","author":"Mosser","year":"2008","journal-title":"Immunol. 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