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In SLE, the triggers are complex and may include both T cell\u2010dependent\/\u2010independent and TLR\u2010dependent\/\u2010independent mechanisms of immune activation, which ultimately contributes to the significant immune dysregulation seen in patients at the level of cytokine production and cellular activation (B cells, T cells, dendritic cells, neutrophils and macrophages). Interferon regulatory factor 5 (\n                    <jats:italic>IRF5<\/jats:italic>\n                    ) has been identified as an autoimmune susceptibility gene and polymorphisms in\n                    <jats:italic>IRF5<\/jats:italic>\n                    associate with altered expression and hyper\u2010activation in distinct SLE immune cell subsets. To gain further insight into the mechanisms that drive IRF5\u2010mediated SLE immune activation, we characterised wild\u2010type (WT) and\n                    <jats:italic>Irf5<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    Balb\/c mice in response to immunisation. WT and\n                    <jats:italic>Irf5<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    Balb\/c mice were immunised to activate various signalling pathways in\u00a0vivo followed by systemic immunophenotyping and detection of antibody production by multi\u2010colour flow cytometry and ELISPOT. We identified two pathways, TLR9\u2010dependent and T cell\u2010dependent that resulted in IRF5 cell type\u2010specific function. Immunisation with either CpG\u2010B\u2009+\u2009Alum or NP\u2010KLH\u2009+\u2009Alum but not with R848\u2009+\u2009Alum, NP\u2010LPS\u2009+\u2009Alum or NP\u2010Ficoll+Alum resulted in decreased plasma cell generation and reduced antibody production in\n                    <jats:italic>Irf5<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. Notably, the mechanism(s) leading to this downstream phenotype was distinct. In CpG\u2010B\u2009+\u2009Alum immunised mice, we found reduced activation of plasmacytoid dendritic cells, resulting in reduced IFN\u03b1 and IL6 production in\n                    <jats:italic>Irf5<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. Conversely, mice immunised with NP\u2010KLH\u2009+\u2009Alum had reduced numbers of T follicular helper cells and germinal centre B cells with reduced expression of Bcl6 in\n                    <jats:italic>Irf5<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. Moreover, T follicular helper cells from\n                    <jats:italic>Irf5<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice were functionally defective. Even though the downstream phenotype of reduced antibody production in\n                    <jats:italic>Irf5<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice was conserved between T cell\u2010dependent and TLR9\u2010dependent immunisation, the mechanisms leading to this phenotype were antigen\u2010 and cell type\u2010specific.\n                  <\/jats:p>","DOI":"10.1111\/imm.13879","type":"journal-article","created":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T00:50:01Z","timestamp":1732236601000},"page":"226-238","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["<scp>IRF5<\/scp>\n                    Controls Plasma Cell Generation and Antibody Production via Distinct Mechanisms Depending on the Antigenic Trigger"],"prefix":"10.1111","volume":"174","author":[{"given":"Bharati","family":"Matta","sequence":"first","affiliation":[{"name":"Center for Autoimmune Musculoskeletal and Hematopoietic Disease The Feinstein Institutes for Medical Research  Manhasset New York USA"},{"name":"Amity Institute of Biotechnology Amity University Rajasthan  Jaipur India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenna","family":"Battaglia","sequence":"additional","affiliation":[{"name":"Center for Autoimmune Musculoskeletal and Hematopoietic Disease The Feinstein Institutes for Medical Research  Manhasset New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Lapan","sequence":"additional","affiliation":[{"name":"Center for Autoimmune Musculoskeletal and Hematopoietic Disease The Feinstein Institutes for Medical Research  Manhasset New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinay","family":"Sharma","sequence":"additional","affiliation":[{"name":"Amity Institute of Biotechnology Amity University Rajasthan  Jaipur India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6766-4352","authenticated-orcid":false,"given":"Betsy J.","family":"Barnes","sequence":"additional","affiliation":[{"name":"Center for Autoimmune Musculoskeletal and Hematopoietic Disease The Feinstein Institutes for Medical Research  Manhasset New York USA"},{"name":"Departments of Pediatrics and Molecular Medicine Donald and Barbara Zucker School of Medicine at Hofstra\/Northwell  Hempstead New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,21]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-014-0440-x"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2020.09.009"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1586\/eci.12.106"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2019.102374"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/0961203318812679"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/715190"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3844\/ajisp.2011.29.38"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)30546-X"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/eci.13032"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2020.102715"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2014.10.003"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-020-00544-4"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1155\/2010\/498980"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2014.05.001"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2015.91"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-012-8270-1"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar2321"},{"issue":"1","key":"e_1_2_9_19_1","first-page":"1","article-title":"Disturbances of Apoptotic Cell Clearance in Systemic Lupus Erythematosus","volume":"13","author":"Shao W. 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