{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T11:45:51Z","timestamp":1790682351751,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,2,25]],"date-time":"2013-02-25T00:00:00Z","timestamp":1361750400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2013,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Hyperactivation of innate immunity by Toll\u2010like receptors (TLRs) can contribute to the development of autoinflammatory or autoimmune diseases. This study evaluated the activation of Tyro3, Axl, Mer (TAM) receptors, physiologic negative regulators of TLRs, by their agonists, growth arrest\u2013specific protein 6 (GAS\u20106) and protein S, in the prevention of collagen\u2010induced arthritis (CIA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Adenoviruses overexpressing GAS\u20106 and protein S were injected intravenously or intraarticularly into mice during CIA. Splenic T helper cell subsets from intravenously injected mice were studied by flow cytometry, and the knee joints of mice injected intravenously and intraarticularly were assessed histologically. Synovium from mice injected intraarticularly was evaluated for cytokine and suppressor of cytokine signaling (SOCS) expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Protein S significantly reduced ankle joint swelling when overexpressed systemically. Further analysis of knee joints revealed a moderate reduction in pathologic changes in the joint and a significant reduction in the number of splenic Th1 cells when protein S was overexpressed systemically. Local overexpression of GAS\u20106 decreased joint inflammation and joint pathology. Protein S treatment showed a similar trend of protection. Consistently, GAS\u20106 and protein S reduced cytokine production in the synovium. Moreover, levels of messenger RNA for interleukin\u201012 (IL\u201012) and IL\u201023 were reduced by GAS\u20106 and protein S treatment, with a corresponding decrease in the production of interferon\u2010\u03b3 and IL\u201017. TAM ligand overexpression was associated with an increase in SOCS\u20103 levels, which likely contributed to the amelioration of arthritis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study provides the first evidence that TAM receptor stimulation by GAS\u20106 and protein S can be used to ameliorate arthritis when applied systemically or locally. TAM receptor stimulation limits proinflammatory signaling and adaptive immunity. This pathway provides a novel strategy by which to combat rheumatoid arthritis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.37786","type":"journal-article","created":{"date-parts":[[2012,11,30]],"date-time":"2012-11-30T16:32:09Z","timestamp":1354293129000},"page":"671-680","source":"Crossref","is-referenced-by-count":67,"title":["Therapeutic efficacy of Tyro3, Axl, and Mer tyrosine kinase agonists in collagen\u2010induced arthritis"],"prefix":"10.1002","volume":"65","author":[{"given":"B. T.","family":"van den Brand","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Abdollahi\u2010Roodsaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. A.","family":"Vermeij","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. B.","family":"Bennink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O. J.","family":"Arntz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. V.","family":"Rothlin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. B.","family":"van den Berg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. A. J.","family":"van de Loo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,2,25]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1061663"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0909610"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90520-0"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.4.2522"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.10.034"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0611289"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2093"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.20678"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar3287"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.22848"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI32639"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M410992200"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-008-1199-1"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.24072"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.70.7.4805-4810.1996"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1101201"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20062293"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1160\/TH11-05-0368"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00311.2010"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.24140"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.2337\/db11-0259"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.5.2813"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2005.02.048"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2006.03.024"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.70.5.708"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/35075603"},{"key":"e_1_2_7_28_2","doi-asserted-by":"crossref","first-page":"3498","DOI":"10.4049\/jimmunol.162.6.3498","article-title":"A novel receptor tyrosine kinase, Mer, inhibits TNF\u2010\u03b1 production and lipopolysaccharide\u2010induced endotoxic shock","volume":"162","author":"Camenisch TD","year":"1999","journal-title":"J Immunol"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65369-2"}],"container-title":["Arthritis &amp; Rheumatism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.37786","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.37786","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T01:31:13Z","timestamp":1697592673000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/art.37786"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,2,25]]},"references-count":28,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2013,3]]}},"alternative-id":["10.1002\/art.37786"],"URL":"https:\/\/doi.org\/10.1002\/art.37786","archive":["Portico"],"relation":{},"ISSN":["0004-3591","1529-0131"],"issn-type":[{"value":"0004-3591","type":"print"},{"value":"1529-0131","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,2,25]]}}}