{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:55:50Z","timestamp":1791356150412,"version":"4.3.1"},"reference-count":39,"publisher":"National Academy of Sciences","issue":"35","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2012,8,28]]},"abstract":"<jats:p>\n                    Interleukin-10 (IL-10) is an important factor involved in T-cell dysfunction during persistent viral infection. Although several factors can negatively regulate T-cell activity, targeting of the IL-10 pathway alone is sufficient to regenerate T-cell activity and increase viral control. How IL-10 mediates these effects is unclear. Here, we investigated the cellular source of IL-10 necessary for establishing T-cell exhaustion and viral persistence, using IL-10 reporter mice (VertX), cell-type\u2013specific IL-10 and IL-10 receptor deletion mice, and bone marrow chimeric mice. During establishment of viral persistence, the cellular subset with the most prevalent expression of IL-10 was CD8\u03b1\n                    <jats:sup>\u2212<\/jats:sup>\n                    CD4\n                    <jats:sup>+<\/jats:sup>\n                    dendritic cells (DCs), which produced IL-10 with increasing kinetics until 9 d postinfection. After this time point, DCs exhibited a modest decline in percentage of IL-10\n                    <jats:sup>+<\/jats:sup>\n                    cells whereas B cells and CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells increased minimally. Further analysis of the DC population demonstrated that IL-10 was primarily expressed in infected DCs. These DCs were a notable source of IL-10 as mutant mice with a DC-specific deletion of IL-10 had significantly decreased serum levels. Interestingly, viral infection was not directly causative of IL-10 expression; rather, IL-10 production appeared to be linked to type I IFN signaling. Our findings further illuminate the contribution of DCs to the production of IL-10 and to viral persistence.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1211910109","type":"journal-article","created":{"date-parts":[[2012,8,15]],"date-time":"2012-08-15T00:12:45Z","timestamp":1344989565000},"page":"14116-14121","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":54,"title":["Infected CD8\u03b1\n                    <sup>\u2212<\/sup>\n                    dendritic cells are the predominant source of IL-10 during establishment of persistent viral infection"],"prefix":"10.1073","volume":"109","author":[{"given":"Cherie T.","family":"Ng","sequence":"first","affiliation":[{"name":"Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael B. A.","family":"Oldstone","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2012,8,14]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1385\/IR:26:1-3:309"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2035"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1492"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20061462"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20071948"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-12-191296"},{"key":"e_1_3_3_7_2","first-page":"1675","article-title":"Circulating IL-2, IL-10 and TNF-alpha in chronic hepatitis B: Their relations to HBeAg status and the activity of liver disease","volume":"47","author":"Bozkaya H","year":"2000","unstructured":"H Bozkaya, et al., Circulating IL-2, IL-10 and TNF-alpha in chronic hepatitis B: Their relations to HBeAg status and the activity of liver disease. Hepatogastroenterology 47, 1675\u20131679 (2000).","journal-title":"Hepatogastroenterology"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(97)80409-6"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.19.1.683"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.6.2978"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2103"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80404-5"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.82238-0"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI20243"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0900185"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1175202"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.189.3.587"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.9.5153"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80059-8"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0914500107"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/25.6.1317"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(01)00227-8"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20041789"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.9.1249"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200939592"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2012.03.009"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20011061"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200323797"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2012.04.016"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.11.6705"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0028432"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1089\/jir.2006.26.893"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.3.1612"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.1.285"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2005.01.005"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-06-027599"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.160.2.521"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.61.5.1571-1576.1987"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2006.02.016"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1211910109","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T21:53:17Z","timestamp":1649800397000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1211910109"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,8,14]]},"references-count":39,"journal-issue":{"issue":"35","published-print":{"date-parts":[[2012,8,28]]}},"alternative-id":["10.1073\/pnas.1211910109"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1211910109","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,8,14]]},"assertion":[{"value":"2012-08-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}