{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:20:27Z","timestamp":1790835627701,"version":"4.1.0"},"reference-count":98,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2020,2,21]],"date-time":"2020-02-21T00:00:00Z","timestamp":1582243200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,6,11]]},"abstract":"<jats:title>Summary<\/jats:title>\n               <jats:p>Toll-like receptors (TLRs) are evolutionarily conserved receptors essential for the host defence against pathogens. Both immune and non-immune cells can express TLRs, although at different levels. Systemic sclerosis (SSc) is a chronic disease in which autoimmunity, dysregulated profibrotic mediator release and activation of fibroblasts lead to dysregulated collagen deposition and fibrosis. There is now increasing knowledge that the innate immune system and, in particular, TLRs take a part in SSc pathogenesis. The list of endogenous ligands that can stimulate TLRs in SSc is growing: these ligands represent specific danger-associated molecular patterns (DAMPs), involved either in the initiation or the perpetuation of inflammation, and in the release of factors that sustain the fibrotic process or directly stimulate the cells that produce collagen and the endothelial cells. This review reports evidences concerning TLR signalling involvement in SSc. We report the new DAMPs, as well as the TLR-linked pathways involved in disease, with emphasis on type I interferon signature in SSc, the role of plasmacytoid dendritic cells (pDCs) and platelets. The dissection of the contribution of all these pathways to disease, and their correlation with the disease status, as well as their values as prognostic tools, can help to plan timely intervention and design new drugs for more appropriate therapeutic strategies.<\/jats:p>","DOI":"10.1111\/cei.13426","type":"journal-article","created":{"date-parts":[[2020,2,12]],"date-time":"2020-02-12T07:24:27Z","timestamp":1581492267000},"page":"14-24","source":"Crossref","is-referenced-by-count":58,"title":["Toll-like receptors in mediating pathogenesis in systemic sclerosis"],"prefix":"10.1093","volume":"201","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6924-3826","authenticated-orcid":false,"given":"L","family":"Frasca","sequence":"first","affiliation":[{"name":"National Centre for Drug Research and Evaluation, Pharmacological Research and Experimental Therapy Unit, Istituto Superiore di Sanit\u00e0, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Lande","sequence":"additional","affiliation":[{"name":"National Centre for Drug Research and Evaluation, Pharmacological Research and Experimental Therapy Unit, Istituto Superiore di Sanit\u00e0, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,2,21]]},"reference":[{"key":"2022011418210709400_cei13426-bib-0001","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1016\/S0140-6736(17)30933-9","article-title":"Systemic sclerosis","volume":"390","author":"Denton","year":"2017","journal-title":"Lancet"},{"key":"2022011418210709400_cei13426-bib-0002","article-title":"Systemic sclerosis: recent insight in clinical management","author":"Zanatta","year":"2019","journal-title":"Joint Bone Spine"},{"key":"2022011418210709400_cei13426-bib-0003","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1093\/rheumatology\/kes090","article-title":"T cells in systemic sclerosis: a reappraisal","volume":"51","author":"O'Reilly","year":"2012","journal-title":"Rheumatology (Oxf)"},{"key":"2022011418210709400_cei13426-bib-0004","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1093\/rheumatology\/ken481","article-title":"Overview of pathogenesis of systemic sclerosis","volume":"48","author":"Abraham","year":"2009","journal-title":"Rheumatology (Oxf)"},{"key":"2022011418210709400_cei13426-bib-0005","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1080\/1744666X.2019.1614915","article-title":"Pathophysiology of systemic sclerosis: current understanding and new insights","volume":"15","author":"Cutolo","year":"2019","journal-title":"Expert Rev Clin Immunol"},{"key":"2022011418210709400_cei13426-bib-0006","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.imlet.2017.09.001","article-title":"Toll-like receptors in systemic sclerosis: an emerging target","volume":"195","author":"O'Reilly","year":"2018","journal-title":"Immunol Lett"},{"key":"2022011418210709400_cei13426-bib-0007","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.3389\/fimmu.2018.01702","article-title":"Innate immunity in systemic sclerosis fibrosis: recent advances","volume":"9","author":"Laurent","year":"2018","journal-title":"Front Immunol"},{"key":"2022011418210709400_cei13426-bib-0008","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1182\/blood-2008-07-019307","article-title":"TLRs and innate immunity","volume":"113","author":"Beutler","year":"2009","journal-title":"Blood"},{"key":"2022011418210709400_cei13426-bib-0009","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1038\/nrrheum.2009.278","article-title":"Sensors of the innate immune system: their link to rheumatic diseases","volume":"6","author":"Theofilopoulos","year":"2010","journal-title":"Nat Rev Rheumatol"},{"key":"2022011418210709400_cei13426-bib-0010","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/s41577-019-0215-7","article-title":"DAMP-sensing receptors in sterile inflammation and inflammatory diseases","volume":"20","author":"Gong","year":"2019","journal-title":"Nat Rev Immunol"},{"key":"2022011418210709400_cei13426-bib-0011","doi-asserted-by":"crossref","first-page":"172487","DOI":"10.1016\/j.ejphar.2019.172487","article-title":"Enlightening the role of high mobility group box 1 (HMGB1) in inflammation: updates on receptor signalling","volume":"858","author":"Paudel","year":"2019","journal-title":"Eur J Pharmacol"},{"key":"2022011418210709400_cei13426-bib-0012","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1038\/ni1457","article-title":"Toll-like receptor 9-dependent activation by DNA-containing immune complexes is mediated by HMGB1 and RAGE","volume":"8","author":"Tian","year":"2007","journal-title":"Nat Immunol"},{"key":"2022011418210709400_cei13426-bib-0013","doi-asserted-by":"crossref","first-page":"eaao3089","DOI":"10.1126\/scitranslmed.aao3089","article-title":"Platelet microparticles sustain autophagy-associated activation of neutrophils in systemic sclerosis","volume":"10","author":"Maugeri","year":"2018","journal-title":"Sci Transl Med"},{"key":"2022011418210709400_cei13426-bib-0014","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/nature08780","article-title":"Circulating mitochondrial DAMPs cause inflammatory responses to injury","volume":"464","author":"Zhang","year":"2010","journal-title":"Nature"},{"key":"2022011418210709400_cei13426-bib-0015","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1146\/annurev.immunol.21.120601.141126","article-title":"Toll-like receptors","volume":"21","author":"Takeda","year":"2003","journal-title":"Annu Rev Immunol"},{"key":"2022011418210709400_cei13426-bib-0016","doi-asserted-by":"crossref","first-page":"7370","DOI":"10.1074\/jbc.M306793200","article-title":"Involvement of toll like receptors 2 and 4 in cellular activation by high mobility group box 1 protein","volume":"279","author":"Park","year":"2004","journal-title":"J Biol Chem"},{"key":"2022011418210709400_cei13426-bib-0017","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1111\/imm.12260","article-title":"Serum amyloid A induces interleukin-6 in dermal fibroblasts via Toll-like receptor 2, interleukin-1 receptor-associated kinase 4 and nuclear factor-\u03baB","volume":"143","author":"O'Reilly","year":"2014","journal-title":"Immunology"},{"key":"2022011418210709400_cei13426-bib-0018","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1136\/ard.43.4.586","article-title":"Serum amyloid A protein concentration in progressive systemic sclerosis (scleroderma)","volume":"43","author":"Brandwein","year":"1984","journal-title":"Ann Rheum Dis"},{"key":"2022011418210709400_cei13426-bib-0019","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1002\/art.33325","article-title":"A rare polymorphism in the gene for Toll-like receptor 2 is associated with systemic sclerosis phenotype and increases the production of inflammatory mediators","volume":"64","author":"Broen","year":"2011","journal-title":"Arthritis Rheum"},{"key":"2022011418210709400_cei13426-bib-0020","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.3008264","article-title":"Fibronectin EDA promotes chronic cutaneous fibrosis through Toll-like receptor signaling","volume":"6","author":"Bhattacharyya","year":"2014","journal-title":"Sci Transl Med"},{"key":"2022011418210709400_cei13426-bib-0021","doi-asserted-by":"crossref","first-page":"11703","DOI":"10.1038\/ncomms11703","article-title":"Tenascin-C drives persistence of organ fibrosis","volume":"7","author":"Bhattacharyya","year":"2016","journal-title":"Nat Commun"},{"key":"2022011418210709400_cei13426-bib-0022","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.98850","article-title":"TLR4-dependent fibroblast activation drives persistent organ fibrosis in skin and lung","volume":"3","author":"Bhattacharyya","year":"2018","journal-title":"JCI Insight"},{"key":"2022011418210709400_cei13426-bib-0023","first-page":"S4","article-title":"The expression profile of the toll-like receptor family in scleroderma dermal fibroblasts","volume":"32","author":"Sakoguchi","year":"2014","journal-title":"Clin Exp Rheumatol"},{"key":"2022011418210709400_cei13426-bib-0024","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1038\/35074106","article-title":"The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5","volume":"410","author":"Hayashi","year":"2001","journal-title":"Nature"},{"key":"2022011418210709400_cei13426-bib-0025","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1038\/cmi.2017.122","article-title":"TLR5: beyond the recognition of flagellin","volume":"14","author":"Yang","year":"2017","journal-title":"Cell Mol Immunol"},{"key":"2022011418210709400_cei13426-bib-0026","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1016\/j.celrep.2016.09.076","article-title":"HMGB1 activates proinflammatory signaling via TLR5 leading to allodynia","volume":"17","author":"Das","year":"2016","journal-title":"Cell Rep"},{"key":"2022011418210709400_cei13426-bib-0027","doi-asserted-by":"crossref","first-page":"475","DOI":"10.4049\/jimmunol.1102977","article-title":"TLR5, a novel and unidentified inflammatory mediator in rheumatoid arthritis that correlates with disease activity score and joint TNF-\u03b1 levels","volume":"189","author":"Charmberlain","year":"2012","journal-title":"J Immunol"},{"key":"2022011418210709400_cei13426-bib-0028","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1038\/s41388-019-1016-y","article-title":"Heat-shock proteins: chaperoning DNA repair","volume":"39","author":"Dubrez","year":"2020","journal-title":"Oncogene"},{"key":"2022011418210709400_cei13426-bib-0029","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1093\/rheumatology\/ken370","article-title":"Proteomic analysis of scleroderma lesional skin reveals activated wound healing phenotype of epidermal cell layer","volume":"47","author":"Aden","year":"2008","journal-title":"Rheumatology"},{"key":"2022011418210709400_cei13426-bib-0030","doi-asserted-by":"crossref","first-page":"2942","DOI":"10.4049\/jimmunol.174.5.2942","article-title":"Human TLR10 is a functional receptor, expressed by B cells and plasmacytoid dendritic cells, which activates gene transcription through MyD88","volume":"174","author":"Hasan","year":"2005","journal-title":"J Immunol"},{"key":"2022011418210709400_cei13426-bib-0031","doi-asserted-by":"crossref","first-page":"516","DOI":"10.3389\/fimmu.2018.00516","article-title":"Recognition of double-stranded RNA and regulation of interferon pathway by toll-like receptor 10","volume":"9","author":"Lee","year":"2018","journal-title":"Front Immunol"},{"key":"2022011418210709400_cei13426-bib-0032","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1016\/j.cell.2019.11.001","article-title":"TLR8 is a sensor of RNase T2 degradation products","volume":"179","author":"Greulich","year":"2019","journal-title":"Cell"},{"key":"2022011418210709400_cei13426-bib-0033","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.it.2019.03.006","article-title":"Cell death and inflammation \u2013 a vital but dangerous liaison","volume":"40","author":"Peltzer","year":"2019","journal-title":"Trends Immunol"},{"key":"2022011418210709400_cei13426-bib-0034","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1038\/s41581-019-0163-2","article-title":"Extracellular DNA traps in inflammation, injury and healing","volume":"15","author":"Daniel","year":"2019","journal-title":"Nat Rev Nephrol"},{"key":"2022011418210709400_cei13426-bib-0035","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.jaut.2009.03.007","article-title":"The genetics and epigenetics of autoimmune diseases","volume":"33","author":"Hewagama","year":"2009","journal-title":"J Autoimmun"},{"key":"2022011418210709400_cei13426-bib-0036","doi-asserted-by":"crossref","first-page":"2163","DOI":"10.1002\/art.23486","article-title":"Induction of interferon-alpha by scleroderma sera containing autoantibodies to topoisomerase I: association of higher interferon-alpha activity with lung fibrosis","volume":"58","author":"Kim","year":"2008","journal-title":"Arthritis Rheum"},{"key":"2022011418210709400_cei13426-bib-0037","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1136\/ard.2009.121400","article-title":"Type I interferon system activation and association with disease manifestations in systemic sclerosis","volume":"69","author":"Eloranta","year":"2010","journal-title":"Ann Rheum Dis"},{"key":"2022011418210709400_cei13426-bib-0038","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1038\/s41467-019-09683-z","article-title":"CXCL4 assembles DNA into liquid crystalline complexes to amplify TLR9-mediated interferon-alpha production in systemic sclerosis","volume":"10","author":"Lande","year":"2019","journal-title":"Nat Commun"},{"key":"2022011418210709400_cei13426-bib-0039","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1186\/s13075-018-1689-6","article-title":"Immune complexes containing scleroderma-specific autoantibodies induce a profibrotic and proinflammatory phenotype in skin fibroblasts","volume":"20","author":"Raschi","year":"2018","journal-title":"Arthritis Res Ther"},{"key":"2022011418210709400_cei13426-bib-0040","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1002\/art.39655","article-title":"Toll-like receptor 9 signaling is augmented in systemic sclerosis and elicits transforming growth factor beta-dependent fibroblast activation","volume":"68","author":"Fang","year":"2016","journal-title":"Arthritis Rheumatol"},{"key":"2022011418210709400_cei13426-bib-0041","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s13353-017-0415-4","article-title":"Expression of TLR7, TLR9, JAK2, and STAT3 genes in peripheral blood mononuclear cells from patients with systemic sclerosis","volume":"59","author":"Vreca","year":"2018","journal-title":"J Appl Genet"},{"key":"2022011418210709400_cei13426-bib-0042","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/s00281-018-0712-y","article-title":"Female predisposition to TLR7-driven autoimmunity: gene dosage and the escape from X chromosome inactivation","volume":"41","author":"Souyris","year":"2018","journal-title":"Semin Immunopathol"},{"key":"2022011418210709400_cei13426-bib-0043","doi-asserted-by":"crossref","first-page":"eaap8855","DOI":"10.1126\/sciimmunol.aap8855","article-title":"TLR7 escapes X chromosome inactivation in immune cells","volume":"3","author":"Souyris","year":"2018","journal-title":"Sci Immunol"},{"key":"2022011418210709400_cei13426-bib-0044","doi-asserted-by":"crossref","first-page":"2583","DOI":"10.1038\/jid.2010.200","article-title":"Poly(I:C) drives type I IFN- and TGFbeta-mediated inflammation and dermal fibrosis simulating altered gene expression in systemic sclerosis","volume":"130","author":"Farina","year":"2010","journal-title":"J Invest Dermatol"},{"key":"2022011418210709400_cei13426-bib-0045","doi-asserted-by":"crossref","first-page":"2956","DOI":"10.4049\/jimmunol.1300376","article-title":"A synthetic TLR3 ligand mitigates profibrotic fibroblast responses by inducing autocrine IFN signaling","volume":"191","author":"Fang","year":"2013","journal-title":"J Immunol"},{"key":"2022011418210709400_cei13426-bib-0046","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1136\/ard.2010.132464","article-title":"dsRNA activation of endothelin-1 and markers of vascular activation in endothelial cells and fibroblasts","volume":"70","author":"Farina","year":"2011","journal-title":"Ann Rheum Dis"},{"key":"2022011418210709400_cei13426-bib-0047","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1002\/art.27224","article-title":"Systemic sclerosis and lupus: points in an interferon-mediated continuum","volume":"62","author":"Assassi","year":"2010","journal-title":"Arthritis Rheum"},{"key":"2022011418210709400_cei13426-bib-0048","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1056\/NEJMoa1114576","article-title":"Proteome-wide analysis and CXCL4 as a biomarker in systemic sclerosis","volume":"370","author":"van Bon","year":"2014","journal-title":"N Engl J Med"},{"key":"2022011418210709400_cei13426-bib-0049","first-page":"154635","article-title":"Type I interferon dysregulation in systemic sclerosis","volume":"23","author":"Skaug","year":"2019","journal-title":"Cytokine"},{"key":"2022011418210709400_cei13426-bib-0050","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cytogfr.2010.10.011","article-title":"The role of the CXC chemokines platelet factor-4 (CXCL4\/PF-4) and its variant (CXCL4L1\/PF-4var) in inflammation, angiogenesis and cancer","volume":"22","author":"Vandercappellen","year":"2011","journal-title":"Cytokine Growth Factor Rev"},{"key":"2022011418210709400_cei13426-bib-0051","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aam8458","article-title":"Plasmacytoid dendritic cells promote systemic sclerosis with a key role for TLR8","volume":"10","author":"Ah Kioon","year":"2018","journal-title":"Sci Transl Med"},{"key":"2022011418210709400_cei13426-bib-0052","doi-asserted-by":"crossref","first-page":"98380","DOI":"10.1172\/jci.insight.98380","article-title":"pDCs in lung and skin fibrosis in a bleomycin-induced model and patients with systemic sclerosis","volume":"3","author":"Kafaja","year":"2018","journal-title":"JCI Insight"},{"key":"2022011418210709400_cei13426-bib-0053","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1038\/nmat4298","article-title":"Liquid-crystalline ordering of antimicrobial peptide-DNA complexes controls TLR9 activation","volume":"14","author":"Schmidt","year":"2015","journal-title":"Nat Mater"},{"key":"2022011418210709400_cei13426-bib-0054","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.semcdb.2018.02.002","article-title":"Modulation of toll-like receptor signaling by antimicrobial peptides","volume":"88","author":"Lee","year":"2019","journal-title":"Semin Cell Dev Biol"},{"key":"2022011418210709400_cei13426-bib-0055","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.autrev.2018.01.012","article-title":"Systemic lupus erythematosus and systemic sclerosis: all roads lead to platelets","volume":"17","author":"Scherlinger","year":"2018","journal-title":"Autoimmun Rev"},{"key":"2022011418210709400_cei13426-bib-0056","first-page":"527","article-title":"Anti-platelet antibodies against gpIIb\/IIIa in systemic sclerosis","volume":"12","author":"Czirjak","year":"1994","journal-title":"Clin Exp Rheumatol"},{"key":"2022011418210709400_cei13426-bib-0057","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1182\/blood-2013-11-536003","article-title":"Platelet-TLR7 mediates host survival and platelet count during viral infection in the absence of platelet-dependent thrombosis","volume":"124","author":"Koupenova","year":"2014","journal-title":"Blood"},{"key":"2022011418210709400_cei13426-bib-0058","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.smim.2009.05.010","article-title":"The role of CD40 and CD40L in dendritic cells","volume":"21","author":"Ma","year":"2009","journal-title":"Semin Immunol"},{"key":"2022011418210709400_cei13426-bib-0059","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1111\/j.1600-065X.2009.00782.x","article-title":"Molecular mechanism and function of CD40\/CD40L engagement in the immune system","volume":"229","author":"Elgueta","year":"2009","journal-title":"Immunol Rev"},{"key":"2022011418210709400_cei13426-bib-0060","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/0268-960X(95)90040-3","article-title":"CD40 and its ligand: central player in B lymphocyte survival, growth and differentiation","volume":"9","author":"Gordon","year":"1995","journal-title":"Blood Rev"},{"key":"2022011418210709400_cei13426-bib-0061","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1093\/rheumatology\/ken270","article-title":"Biomarkers in systemic sclerosis","volume":"47","author":"Doran","year":"2008","journal-title":"Rheumatology"},{"key":"2022011418210709400_cei13426-bib-0062","doi-asserted-by":"crossref","first-page":"83","DOI":"10.3389\/fimmu.2015.00083","article-title":"The inflammatory role of platelets via their TLRs and Siglec receptors","volume":"6","author":"Cognasse","year":"2015","journal-title":"Front Immunol"},{"key":"2022011418210709400_cei13426-bib-0063","doi-asserted-by":"crossref","first-page":"4317","DOI":"10.1182\/blood-2010-01-261206","article-title":"Platelet CD40L mediates thrombotic and inflammatory processes in atherosclerosis","volume":"116","author":"Lievenss","year":"2010","journal-title":"Blood"},{"key":"2022011418210709400_cei13426-bib-0064","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s11926-019-0815-z","article-title":"Platelets in systemic sclerosis: the missing link connecting vasculopathy, autoimmunity, and fibrosis?","volume":"21","author":"Ntelis","year":"2019","journal-title":"Curr Rheumatol Rep"},{"key":"2022011418210709400_cei13426-bib-0065","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1097\/MBC.0b013e328010bd05","article-title":"Increased circulating platelet\u2013leucocyte complexes in patients with primary Raynaud's phenomenon and Raynaud's phenomenon secondary to systemic sclerosis: a comparative study","volume":"18","author":"Pamuk","year":"2007","journal-title":"Blood Coagul Fibrinolysis"},{"key":"2022011418210709400_cei13426-bib-0066","doi-asserted-by":"crossref","first-page":"312","DOI":"10.3109\/09537104.2011.618563","article-title":"Increased mean platelet volume in primary Raynaud's phenomenon","volume":"23","author":"Shemirani","year":"2011","journal-title":"Platelets"},{"key":"2022011418210709400_cei13426-bib-0067","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/nature21706","article-title":"The lung is a site of platelet biogenesis and a reservoir for haematopoietic progenitors","volume":"544","author":"Lefrancais","year":"2017","journal-title":"Nature"},{"key":"2022011418210709400_cei13426-bib-0068","doi-asserted-by":"crossref","first-page":"2173","DOI":"10.1182\/blood-2014-05-573543","article-title":"Platelets release mitochondria serving as substrate for bactericidal group IIA-secreted phospholipase A2 to promote inflammation","volume":"124","author":"Boudreau","year":"2014","journal-title":"Blood"},{"key":"2022011418210709400_cei13426-bib-0069","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1038\/nature06116","article-title":"Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide","volume":"449","author":"Lande","year":"2007","journal-title":"Nature"},{"key":"2022011418210709400_cei13426-bib-0070","doi-asserted-by":"crossref","first-page":"1983","DOI":"10.1084\/jem.20090480","article-title":"Self-RNA-antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8","volume":"206","author":"Ganguly","year":"2009","journal-title":"J Exp Med"},{"key":"2022011418210709400_cei13426-bib-0071","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1111\/j.1600-0625.2011.01327.x","article-title":"LL-37 suppresses sodium nitroprusside-induced apoptosis of systemic sclerosis dermal fibroblasts","volume":"20","author":"Kim","year":"2011","journal-title":"Exp Dermatol"},{"key":"2022011418210709400_cei13426-bib-0072","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1111\/bjd.14699","article-title":"A potential contribution of antimicrobial peptide LL-37 to tissue fibrosis and vasculopathy in systemic sclerosis","volume":"175","author":"Takahashi","year":"2016","journal-title":"Br J Dermatol"},{"key":"2022011418210709400_cei13426-bib-0073","doi-asserted-by":"crossref","first-page":"865","DOI":"10.4049\/jimmunol.1201648","article-title":"\u03b2-defensin 2 and 3 promote the uptake of self or CpG DNA, enhance IFN-\u03b1 production by human plasmacytoid dendritic cells, and promote inflammation","volume":"191","author":"Tewary","year":"2013","journal-title":"J Immunol"},{"key":"2022011418210709400_cei13426-bib-0074","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1002\/eji.201344277","article-title":"Cationic antimicrobial peptides in psoriatic skin cooperate to break innate tolerance to self-DNA","volume":"45","author":"Lande","year":"2015","journal-title":"Eur J Immunol"},{"key":"2022011418210709400_cei13426-bib-0075","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1038\/ni.3211","article-title":"TH17 cells promote microbial killing and innate immune sensing of DNA via interleukin 26","volume":"16","author":"Meller","year":"2015","journal-title":"Nat Immunol"},{"key":"2022011418210709400_cei13426-bib-0076","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1111\/j.1365-2133.2006.07391.x","article-title":"Ultraviolet Al-induced downregulation of human beta-defensins and interleukin-6 and interleukin-8 correlates with clinical improvement in localized scleroderma","volume":"155","author":"Kreuter","year":"2006","journal-title":"Br J Dermatol"},{"key":"2022011418210709400_cei13426-bib-0077","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1002\/1529-0131(199902)42:2<299::AID-ANR12>3.0.CO;2-R","article-title":"Interferon-alpha does not improve outcome at one year in patients with diffuse cutaneous scleroderma: results of a randomized, double-blind, placebo-controlled trial","volume":"42","author":"Black","year":"1999","journal-title":"Arthritis Rheum"},{"key":"2022011418210709400_cei13426-bib-0078","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1046\/j.1365-2133.2002.48901.x","article-title":"Systemic sclerosis after interferon-alfa therapy for myeloproliferative disorders","volume":"147","author":"Beretta","year":"2002","journal-title":"Br J Dermatol"},{"key":"2022011418210709400_cei13426-bib-0079","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1007\/s10067-008-0972-3","article-title":"The development of systemic sclerosis in a female patient with multiple sclerosis following beta interferon treatment","volume":"27","author":"Powell","year":"2008","journal-title":"Clin Rheumatol"},{"key":"2022011418210709400_cei13426-bib-0080","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1136\/annrheumdis-2015-207392","article-title":"The interferon type I signature is present in systemic sclerosis before overt fibrosis and might contribute to its pathogenesis through high BAFF gene expression and high collagen synthesis","volume":"75","author":"Brkic","year":"2016","journal-title":"Ann Rheum Dis"},{"key":"2022011418210709400_cei13426-bib-0081","doi-asserted-by":"crossref","first-page":"4794","DOI":"10.4049\/jimmunol.1000702","article-title":"Mechanism of endosomal TLR inhibition by antimalarial drugs and imidazoquinolines","volume":"186","author":"Kuznik","year":"2011","journal-title":"J Immunol"},{"key":"2022011418210709400_cei13426-bib-0082","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1136\/annrheumdis-2019-215208","article-title":"Interferon regulatory factor 7 (IRF7) represents a link between inflammation and fibrosis in the pathogenesis of systemic sclerosis","volume":"78","author":"Wu","year":"2019","journal-title":"Ann Rheum Dis"},{"key":"2022011418210709400_cei13426-bib-0083","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/S1089-3261(02)00024-7","article-title":"Autoimmunity and viruses","volume":"6","author":"Vogel","year":"2002","journal-title":"Clin Liver Dis"},{"key":"2022011418210709400_cei13426-bib-0084","doi-asserted-by":"crossref","first-page":"E762","DOI":"10.3390\/v11080762","article-title":"Viruses and autoimmunity: a review on the potential interaction and molecular mechanisms","volume":"11","author":"Smatti","year":"2019","journal-title":"Viruses"},{"key":"2022011418210709400_cei13426-bib-0085","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1177\/1073858410386615","article-title":"Viruses and multiple sclerosis","volume":"17","author":"Owens","year":"2012","journal-title":"Neuroscientist"},{"key":"2022011418210709400_cei13426-bib-0086","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/s10238-018-0535-0","article-title":"The risk of systemic lupus erythematosus associated with Epstein\u2013Barr virus infection: a systematic review and meta-analysis","volume":"19","author":"Li","year":"2018","journal-title":"Clin Exp Med"},{"key":"2022011418210709400_cei13426-bib-0087","first-page":"539282","article-title":"Autoimmunity in rheumatic diseases is induced by microbial infections via crossreactivity or molecular mimicry","volume":"21","author":"Rashid","year":"2012","journal-title":"Autoimmune Dis"},{"key":"2022011418210709400_cei13426-bib-0088","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.autrev.2008.07.022","article-title":"Systemic sclerosis and infections","volume":"8","author":"Randone","year":"2008","journal-title":"Autoimmun Rev"},{"key":"2022011418210709400_cei13426-bib-0089","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s13075-017-1237-9","article-title":"Epstein\u2013Barr virus lytic infection promotes activation of Toll-like receptor 8 innate immune response in systemic sclerosis monocytes","volume":"19","author":"Farina","year":"2017","journal-title":"Arthritis Res Ther"},{"key":"2022011418210709400_cei13426-bib-0090","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1038\/jid.2013.423","article-title":"Epstein\u2013Barr virus infection induces aberrant TLR activation pathway and fibroblast\u2013myofibroblast conversion in scleroderma","volume":"134","author":"Farina","year":"2014","journal-title":"J Invest Dermatol"},{"key":"2022011418210709400_cei13426-bib-0091","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.micpath.2018.04.041","article-title":"Cytomegalovirus aggravates the autoimmune phenomenon in systemic autoimmune diseases","volume":"120","author":"Janahi","year":"2018","journal-title":"Microb Pathog"},{"key":"2022011418210709400_cei13426-bib-0092","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.clim.2019.07.012","article-title":"A comprehensive analysis of antigen-specific antibody responses against human cytomegalovirus in patients with systemic sclerosis","volume":"207","author":"Efthymiou","year":"2019","journal-title":"Clin Immunol"},{"key":"2022011418210709400_cei13426-bib-0093","doi-asserted-by":"crossref","first-page":"2125","DOI":"10.1016\/j.jid.2019.03.1144","article-title":"Effects of parvovirus B19 in vitro infection on monocytes from patients with systemic sclerosis: enhanced inflammatory pathways by caspase-1 activation and cytokine production","volume":"139","author":"Zakrzewska","year":"2019","journal-title":"J Invest Dermatol"},{"key":"2022011418210709400_cei13426-bib-0094","doi-asserted-by":"crossref","first-page":"248","DOI":"10.4049\/jimmunol.1601968","article-title":"The activation of human dermal microvascular cells by Poly(I:C), lipopolysaccharide, imiquimod, and ODN2395 is mediated by the Fli1\/FOXO3A pathway","volume":"200","author":"Stawski","year":"2018","journal-title":"J Immunol"},{"key":"2022011418210709400_cei13426-bib-0095","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1128\/CVI.00257-07","article-title":"Human skin endothelial cells can express all 10 TLR genes and respond to respective ligands","volume":"15","author":"Fitzner","year":"2008","journal-title":"Clin Vacc Immunol"},{"key":"2022011418210709400_cei13426-bib-0096","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1002\/jcp.22454","article-title":"Toll-like receptors expressed by dermal fibroblasts contribute to hypertrophic scarring","volume":"226","author":"Wang","year":"2011","journal-title":"J Cell Physiol"},{"key":"2022011418210709400_cei13426-bib-0097","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.3892\/ijmm.2015.2146","article-title":"Toll-like receptor family members in skin fibroblasts are functional and have a higher expression compared to skin keratinocytes","volume":"35","author":"Yao","year":"2015","journal-title":"Int J Mol Med"},{"key":"2022011418210709400_cei13426-bib-0098","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1111\/1348-0421.12022","article-title":"Interleukin-8 and CXCL10 expression in oral keratinocytes and fibroblasts via Toll-like receptors","volume":"57","author":"Fukui","year":"2013","journal-title":"Microbiol Immunol"}],"container-title":["Clinical and Experimental Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcei.13426","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cei.13426","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cei.13426","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/201\/1\/14\/42195740\/cei13426.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/201\/1\/14\/42195740\/cei13426.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,14]],"date-time":"2022-01-14T19:06:08Z","timestamp":1642187168000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cei\/article\/201\/1\/14\/6401617"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,21]]},"references-count":98,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,2,21]]},"published-print":{"date-parts":[[2020,6,11]]}},"URL":"https:\/\/doi.org\/10.1111\/cei.13426","relation":{},"ISSN":["0009-9104","1365-2249"],"issn-type":[{"value":"0009-9104","type":"print"},{"value":"1365-2249","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,7]]},"published":{"date-parts":[[2020,2,21]]}}}