{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T17:27:38Z","timestamp":1783445258376,"version":"3.54.6"},"reference-count":55,"publisher":"Portland Press Ltd.","issue":"8","license":[{"start":{"date-parts":[[2020,7,29]],"date-time":"2020-07-29T00:00:00Z","timestamp":1595980800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,8,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Mef2 transcription factors comprise a family of four different isoforms that regulate a number of processes including neuronal and muscle development. While roles for Mef2C and Mef2D have been described in B-cell development their role in immunity has not been extensively studied. In innate immune cells such as macrophages, TLRs drive the production of both pro- and anti-inflammatory cytokines. IL-10 is an important anti-inflammatory cytokine produced by macrophages and it establishes an autocrine feedback loop to inhibit pro-inflammatory cytokine production. We show here that macrophages from Mef2D knockout mice have elevated levels of IL-10 mRNA induction compared with wild-type cells following LPS stimulation. The secretion of IL-10 was also higher from Mef2D knockout macrophages and this correlated to a reduction in the secretion of TNF, IL-6 and IL-12p40. The use of an IL-10 neutralising antibody showed that this reduction in pro-inflammatory cytokine production in the Mef2D knockouts was IL-10 dependent. As the IL-10 promoter has previously been reported to contain a potential binding site for Mef2D, it is possible that the binding of other Mef2 isoforms in the absence of Mef2D may result in a higher activation of the IL-10 gene. Further studies with compound Mef2 isoforms would be required to address this. We also show that Mef2D is highly expressed in the thymus, but that loss of Mef2D does not affect thymic T-cell development or the production of IFN\u03b3 from CD8 T cells.<\/jats:p>","DOI":"10.1042\/bsr20201859","type":"journal-article","created":{"date-parts":[[2020,7,29]],"date-time":"2020-07-29T11:36:17Z","timestamp":1596022577000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Loss of Mef2D function enhances TLR induced IL-10 production in macrophages"],"prefix":"10.1042","volume":"40","author":[{"given":"Michael\u00a0J.","family":"Pattison","sequence":"first","affiliation":[{"name":"Division of Cell Signalling and Immunology, Wellcome Trust Building, School of Life Sciences, University of Dundee, Dow St, Dundee, DD5 1EH, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rangeetha\u00a0Jayaprakash","family":"Naik","sequence":"additional","affiliation":[{"name":"Division of Cell Signalling and Immunology, Wellcome Trust Building, School of Life Sciences, University of Dundee, Dow St, Dundee, DD5 1EH, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen\u00a0M.S.E.","family":"Reyskens","sequence":"additional","affiliation":[{"name":"Division of Cell Signalling and Immunology, Wellcome Trust Building, School of Life Sciences, University of Dundee, Dow St, Dundee, DD5 1EH, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8135-1958","authenticated-orcid":false,"given":"J. Simon\u00a0C.","family":"Arthur","sequence":"additional","affiliation":[{"name":"Division of Cell Signalling and Immunology, Wellcome Trust Building, School of Life Sciences, University of Dundee, Dow St, Dundee, DD5 1EH, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2020,8,21]]},"reference":[{"key":"2021111620233662900_B1","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1038\/nri3495","article-title":"Mitogen-activated protein kinases in innate immunity","volume":"13","author":"Arthur","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"2021111620233662900_B2","doi-asserted-by":"publisher","first-page":"2383","DOI":"10.1242\/jcs.149831","article-title":"The TLR and IL-1 signalling network at a glance","volume":"127","author":"Cohen","year":"2014","journal-title":"J. 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