{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T19:41:06Z","timestamp":1792179666353,"version":"4.4.0"},"reference-count":84,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T00:00:00Z","timestamp":1741305600000},"content-version":"vor","delay-in-days":3506,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>IL-10 is produced by macrophages in diverse immune settings and is critical in limiting immune-mediated pathology. In helminth infections, macrophages are an important source of IL-10; however, the molecular mechanism underpinning production of IL-10 by these cells is poorly characterized. In this study, bone marrow\u2013derived macrophages exposed to excretory\/secretory products released by Schistosoma mansoni cercariae rapidly produce IL-10 as a result of MyD88-mediated activation of MEK\/ERK\/RSK and p38. The phosphorylation of these kinases was triggered by TLR2 and TLR4 and converged on activation of the transcription factor CREB. Following phosphorylation, CREB is recruited to a novel regulatory element in the Il10 promoter and is also responsible for regulating a network of genes involved in metabolic processes, such as glycolysis, the tricarboxylic acid cycle, and oxidative phosphorylation. Moreover, skin-resident tissue macrophages, which encounter S. mansoni excretory\/secretory products during infection, are the first monocytes to produce IL-10 in vivo early postinfection with S. mansoni cercariae. The early and rapid release of IL-10 by these cells has the potential to condition the dermal microenvironment encountered by immune cells recruited to this infection site, and we propose a mechanism by which CREB regulates the production of IL-10 by macrophages in the skin, but also has a major effect on their metabolic state.<\/jats:p>","DOI":"10.4049\/jimmunol.1500146","type":"journal-article","created":{"date-parts":[[2015,6,27]],"date-time":"2015-06-27T12:26:16Z","timestamp":1435407976000},"page":"1218-1232","source":"Crossref","is-referenced-by-count":119,"title":["IL-10 Production in Macrophages Is Regulated by a TLR-Driven CREB-Mediated Mechanism That Is Linked to Genes Involved in Cell Metabolism"],"prefix":"10.1093","volume":"195","author":[{"given":"David E","family":"Sanin","sequence":"first","affiliation":[{"name":"Department of Biology, Centre for Immunology and Infection, University of York , York YO10 5DD ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catriona T","family":"Prendergast","sequence":"additional","affiliation":[{"name":"Department of Biology, Centre for Immunology and Infection, University of York , York YO10 5DD ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian P","family":"Mountford","sequence":"additional","affiliation":[{"name":"Department of Biology, Centre for Immunology and Infection, University of York , York YO10 5DD ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,8,1]]},"reference":[{"key":"2025030703575448200_r1","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1111\/pim.12113","article-title":"Protection and pathology during parasite infection: IL-10 strikes the balance","volume":"36","author":"Redpath","year":"2014","journal-title":"Parasite Immunol."},{"key":"2025030703575448200_r2","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1016\/S0140-6736(00)03206-2","article-title":"Decreased atopy in children infected with Schistosoma haematobium: a role for parasite-induced interleukin-10","volume":"356","author":"van den Biggelaar","year":"2000","journal-title":"Lancet"},{"key":"2025030703575448200_r3","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1186\/1471-2334-7-139","article-title":"Cytokine responses to Schistosoma haematobium in a Zimbabwean population: contrasting profiles for IFN-gamma, IL-4, IL-5 and IL-10 with age","volume":"7","author":"Mutapi","year":"2007","journal-title":"BMC Infect. 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