{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:12:17Z","timestamp":1790874737063,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T00:00:00Z","timestamp":1730678400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004755","name":"EMD Serono","doi-asserted-by":"publisher","award":["CrossRef Funder ID: 10.13039\/100004755"],"award-info":[{"award-number":["CrossRef Funder ID: 10.13039\/100004755"]}],"id":[{"id":"10.13039\/100004755","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Activation of endosomal toll\u2010like receptors (TLRs) is one possible driver of inflammation in idiopathic inflammatory myopathies (IIM). We investigated the potential contribution of TLR7 and TLR8 to IIM pathogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Activation of TLR7\/8 in healthy donor peripheral blood mononuclear cells (PBMCs) by immune complexes from patients with IIMs and lupus was tested. Autoantibody profiling of patient IgG samples was performed using a 1581 antigen array. TLR7 and\/or TLR8 activation by RNA molecules associated with autoantibodies was assessed. Gene expression in human myoblasts and satellite cells following treatment with supernatants from TLR7\/8\u2010activated PBMCs was evaluated by NanoString. C57BL\/6 mice were dosed intramuscularly with the TLR7\/8 agonist R848 and single\u2010cell RNA\u2010sequencing was performed on the muscle to ascertain the cell types responding to TLR7\/8 activation and the downstream effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Overall, 69 patients with IIMs were included with representation of dermatomyositis, polymyositis, and inclusion body myositis subsets. Immune complexes from patients with IIMs, as well as autoantibody\u2010associated RNAs histidyl\u2010transfer RNA, Y1, Y4, and U1, activated PBMCs to produce interferon\u2010\u03b1 and IL\u20106 via TLR7\/8. Several canonical (Ro60, Ro52, and HIST1H4A) and novel (IL\u201036RN) autoreactivities correlated highly with TLR7\/8 activation. Supernatants from TLR7\/8\u2010activated PBMCs had a negative impact on human myoblasts and satellite cells. Endothelial cells were activated by R848 in mouse muscle in vivo in addition to immune cells such as monocytes and macrophages.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our results suggest that patients with IIMs have autoantibodies in their blood causing TLR7\/8 activation, which leads to inflammation in muscles with potential deleterious effects.<\/jats:p>\n                    <jats:p>\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/art42989-toc-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n      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