{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T02:29:19Z","timestamp":1790994559470,"version":"4.1.0"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":160,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI070101, DK083356"],"award-info":[{"award-number":["AI070101, DK083356"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2015,6]]},"abstract":"<jats:p>\n                    Chronic liver disease mediated by activation of hepatic stellate cells (HSCs) leads to liver fibrosis. Here, we postulated that the immune regulatory properties of HSCs might promote the profibrogenic activity of B cells. Fibrosis is completely attenuated in carbon tetrachloride\u2013treated, B cell\u2013deficient \u00b5MT mice, showing that B cells are required. The retinoic acid produced by HSCs augmented B\u2010cell survival, plasma cell marker CD138 expression, and immunoglobulin G production. These activities were reversed following addition of the retinoic acid inhibitor LE540. Transcriptional profiling of fibrotic liver B cells revealed increased expression of genes related to activation of nuclear factor \u03ba light chain enhancer of activated B cells, proinflammatory cytokine production, and CD40 signaling, suggesting that these B cells are activated and may be acting as inflammatory cells. Biological validation experiments also revealed increased activation (CD44 and CD86 expression), constitutive immunoglobulin G production, and secretion of the proinflammatory cytokines tumor necrosis factor\u2010\u03b1, monocyte chemoattractant protein\u20101, and macrophage inflammatory protein\u20101\u03b1. Likewise, targeted deletion of B\u2010cell\u2010intrinsic myeloid differentiation primary response gene 88 signaling, an innate adaptor with involvement in retinoic acid signaling, resulted in reduced infiltration of migratory CD11c\n                    <jats:sup>+<\/jats:sup>\n                    dendritic cells and Ly6C\n                    <jats:sup>++<\/jats:sup>\n                    monocytes and, hence, reduced liver pathology.\n                    <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>\n                    : Liver fibrosis occurs through a mechanism of HSC\u2010mediated augmentation of innate B\u2010cell activity. These findings highlight B cells as important \u201cfirst responders\u201d of the intrahepatic immune environment. (H\n                    <jats:sc>epatology<\/jats:sc>\n                    2015;61:2067\u20102079)\n                  <\/jats:p>","DOI":"10.1002\/hep.27761","type":"journal-article","created":{"date-parts":[[2015,2,24]],"date-time":"2015-02-24T19:04:54Z","timestamp":1424804694000},"page":"2067-2079","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":97,"title":["Liver fibrosis occurs through dysregulation of MyD88\u2010dependent innate B\u2010cell activity"],"prefix":"10.1097","volume":"61","author":[{"given":"Manoj","family":"Thapa","sequence":"first","affiliation":[{"name":"Emory Vaccine Center,Division of Microbiology and Immunology,Emory University School of Medicine,Atlanta,GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raghavan","family":"Chinnadurai","sequence":"additional","affiliation":[{"name":"Emory Vaccine Center,Division of Microbiology and Immunology,Emory University School of 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