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In systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis, NA\u2010containing immune complexes serve as TLR ligands, with distinct implications depending on the additional immune stimuli available. Plasmacytoid dendritic cells (pDCs), the robust producers of type I interferon (IFN\u2010I), are providing critical insights relevant to TLR\u2010mediated healthy immune responses and tissue repair, as well as generation of inflammation, autoimmunity and fibrosis, processes central to the pathogenesis of many autoimmune diseases. In this review, we describe recent data characterizing the role of platelets and NA\u2010binding chemokines in modulation of TLR signaling in pDCs, as well as implications for how the IFN\u2010I products of pDCs contribute to the generation of inflammation and wound healing responses by monocyte\/macrophages. Chemokine modulators of TLR\u2010mediated B cell tolerance mechanisms and interactions between TLR signaling and metabolic pathways are also considered. The modulators of TLR signaling and their contribution to the pathogenesis of systemic autoimmune diseases suggest new opportunities for identification of novel therapeutic targets.<\/jats:p>","DOI":"10.1111\/imr.13331","type":"journal-article","created":{"date-parts":[[2024,3,30]],"date-time":"2024-03-30T04:07:30Z","timestamp":1711771650000},"page":"241-256","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Modulation of plasmacytoid dendritic cells response in inflammation and autoimmunity"],"prefix":"10.1111","volume":"323","author":[{"given":"Marie Dominique","family":"Ah Kioon","sequence":"first","affiliation":[{"name":"HSS Research Institute Hospital for Special Surgery  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7102-2184","authenticated-orcid":false,"given":"Pa\u00f4line","family":"Laurent","sequence":"additional","affiliation":[{"name":"HSS Research Institute Hospital for Special Surgery  New York New York USA"},{"name":"Department of Microbiology and Immunology Weill Cornell Medical College of Cornell University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vidyanath","family":"Chaudhary","sequence":"additional","affiliation":[{"name":"HSS Research Institute Hospital for Special Surgery  New York New York USA"},{"name":"Department of Microbiology and Immunology Weill Cornell Medical College of Cornell University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Du","sequence":"additional","affiliation":[{"name":"HSS Research Institute Hospital for Special Surgery  New York New York USA"},{"name":"Department of Microbiology and Immunology Weill Cornell Medical College of Cornell University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary K.","family":"Crow","sequence":"additional","affiliation":[{"name":"HSS Research Institute Hospital for Special Surgery  New York New York USA"},{"name":"Mary Kirkland Center for Lupus Research Hospital for Special Surgery  New York New York USA"},{"name":"Department of Medicine Weill Cornell Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0735-0850","authenticated-orcid":false,"given":"Franck J.","family":"Barrat","sequence":"additional","affiliation":[{"name":"HSS Research Institute Hospital for Special Surgery  New York New York USA"},{"name":"Department of Microbiology and Immunology Weill Cornell Medical College of Cornell University  New York New York USA"},{"name":"David Z. 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