{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T02:28:05Z","timestamp":1790130485900,"version":"4.0.1"},"reference-count":62,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2016,10,26]]},"abstract":"\n Background<\/jats:title>\n \n We previously identified peritoneal B1a cells that secrete natural IgM as a key atheroprotective B cell subset. However, the molecules that activate atheroprotective B1a cells are unknown. Here, we investigated whether Toll\u2010like receptors (TLRs)\n TLR<\/jats:styled-content>\n 2,\n TLR<\/jats:styled-content>\n 4, and\n TLR<\/jats:styled-content>\n 9 expressed by B1a cells are required for IgM\u2010mediated atheroprotection.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n We adoptively transferred B1a cells from wild\u2010type mice or from mice deficient in\n TLR<\/jats:styled-content>\n 2,\n TLR<\/jats:styled-content>\n 4,\n TLR<\/jats:styled-content>\n 9, or myeloid differentiation primary response 88 (MyD88) into ApoE\n \u2212\/\u2212<\/jats:sup>\n mice depleted of peritoneal B1a cells by splenectomy and fed a high\u2010fat diet for 8\u00a0weeks. Elevations in plasma total, anti\u2010oxLDL (oxidized low\u2010density lipoprotein), anti\u2010leukocyte, anti\u2010\n CD<\/jats:styled-content>\n 3, anti\u2010\n CD<\/jats:styled-content>\n 8, and anti\u2010\n CD<\/jats:styled-content>\n 4 IgMs in atherosclerotic mice required B1a cells expressing\n TLR<\/jats:styled-content>\n 4 and MyD88, indicating a critical role for\n TLR<\/jats:styled-content>\n 4\u2010MyD88 signaling for IgM secretion. Suppression of atherosclerosis was also critically dependent on B1a cells expressing\n TLR<\/jats:styled-content>\n 4\u2010MyD88. Atherosclerosis suppression was associated not only with reductions in lesion apoptotic cells, necrotic cores, and ox\n LDL<\/jats:styled-content>\n , but also with reduced lesion\n CD<\/jats:styled-content>\n 4\n +<\/jats:sup>\n and\n CD<\/jats:styled-content>\n 8\n +<\/jats:sup>\n T cells. Transforming growth factor beta 1 (\n TGF<\/jats:styled-content>\n \u2010\u03b21) expression, including macrophages expressing\n TGF<\/jats:styled-content>\n \u2010\u03b21, was increased, consistent with increased IgM\u2010mediated phagocytosis of apoptotic cells by macrophages. Reductions in lesion inflammatory cytokines tumor necrosis factor alpha (\n TNF<\/jats:styled-content>\n \u2010\u03b1), interleukin (\n IL)<\/jats:styled-content>\n 1\u03b2, and\n IL<\/jats:styled-content>\n \u201018 were consistent with augmented\n TGF<\/jats:styled-content>\n \u2010\u03b21 expression.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n TLR<\/jats:styled-content>\n 4\u2010MyD88 expression on B1a cells is critical for their IgM\u2010dependent atheroprotection that not only reduced lesion apoptotic cells and necrotic cores, but also decreased\n CD<\/jats:styled-content>\n 4 and\n CD<\/jats:styled-content>\n 8 T\u2010cell infiltrates and augmented\n TGF<\/jats:styled-content>\n \u2010\u03b21 expression accompanied by reduced lesion inflammatory cytokines\n TNF<\/jats:styled-content>\n \u2010\u03b1,\n IL<\/jats:styled-content>\n \u20101\u03b2, and\n IL<\/jats:styled-content>\n \u201018.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.115.002947","type":"journal-article","created":{"date-parts":[[2016,11,15]],"date-time":"2016-11-15T02:25:27Z","timestamp":1479176727000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":33,"title":["Toll\u2010Like Receptor (TLR)4 and MyD88 are Essential for Atheroprotection by Peritoneal B1a B Cells"],"prefix":"10.1161","volume":"5","author":[{"given":"Hamid","family":"Hosseini","sequence":"first","affiliation":[{"name":"BakerIDI heart and Diabetes Institute, Melbourne, Australia"},{"name":"Department of Medicine, Centre for Inflammatory Diseases, Southern Clinical School, Clayton, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Li","sequence":"additional","affiliation":[{"name":"BakerIDI heart and Diabetes Institute, Melbourne, Australia"},{"name":"Department of Medicine, Centre for Inflammatory Diseases, Southern Clinical School, Clayton, 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