{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T03:22:47Z","timestamp":1793071367756,"version":"4.5.0"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T00:00:00Z","timestamp":1770681600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T00:00:00Z","timestamp":1770681600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Immunol"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Recognition of RNA fragments by Toll-like receptor 7 (TLR7) and TLR8 helps to initiate the innate immune response against pathogens. An outstanding question is why RNA fragments generated during clearance of apoptotic cells fail to activate TLR7 and TLR8 signaling. Here we show that select 2\u2032-\n                    <jats:italic>O<\/jats:italic>\n                    -methyl (2\u2032-OMe) guanosine RNA fragments, including those derived from host RNAs, function as potent TLR7 and TLR8 antagonists and reduce TLR7 sensing in vivo. Mechanistically, these fragments bind to an antagonistic site on these proteins via their 5\u2032-end 2\u2032-OMe guanosine. These findings indicate that host RNAs evade detection because abundant ribosomal 2\u2032-OMe-modified fragments naturally antagonize TLR7 and TLR8. Crucially, rare TLR7 and TLR8 mutations at this antagonist binding site decrease inhibition by 2\u2032-OMe guanosine RNA fragments, leading to autoimmunity in patients. Collectively, this work redefines TLR7 and TLR8 sensing by introducing 2\u2032-OMe guanosine as a natural immune checkpoint for their activation.\n                  <\/jats:p>","DOI":"10.1038\/s41590-026-02429-2","type":"journal-article","created":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T10:03:30Z","timestamp":1770717810000},"page":"762-775","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["2\u2032-O-Methyl-guanosine RNA fragments antagonize TLR7 and TLR8 to limit autoimmunity"],"prefix":"10.1038","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3694-1067","authenticated-orcid":false,"given":"Arwaf S.","family":"Alharbi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7901-9879","authenticated-orcid":false,"given":"Sunil","family":"Sapkota","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhikuan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruitao","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erandi","family":"Rupasinghe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. Samantha N.","family":"Jayasekara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dingyi","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Speir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorna","family":"Wilkinson-White","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liza","family":"Cubeddu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6301-2533","authenticated-orcid":false,"given":"Julia I.","family":"Ellyard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2859-2461","authenticated-orcid":false,"given":"Refaya","family":"Rezwan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel S.","family":"Wenholz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8545-8285","authenticated-orcid":false,"given":"Alexandra L.","family":"McAllan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le","family":"Ying","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasan M.","family":"Sathiqu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hani","family":"Hosseini Far","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josiah","family":"Bones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sitong","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina R.","family":"Alexander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim A.","family":"Lennox","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1373-8472","authenticated-orcid":false,"given":"Paul J.","family":"Hertzog","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7439-3834","authenticated-orcid":false,"given":"Claudia A.","family":"Nold-Petry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cameron R.","family":"Stewart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9799-0298","authenticated-orcid":false,"given":"Carola G.","family":"Vinuesa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Behlke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umeharu","family":"Ohto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0966-9897","authenticated-orcid":false,"given":"Olivier F.","family":"Laczka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Gamsjaeger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6324-442X","authenticated-orcid":false,"given":"Ben","family":"Corry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0547-8922","authenticated-orcid":false,"given":"Toshiyuki","family":"Shimizu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3740-698X","authenticated-orcid":false,"given":"Michael P.","family":"Gantier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,10]]},"reference":[{"key":"2429_CR1","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1126\/sciimmunol.abl4348","volume":"6","author":"T Asano","year":"2021","unstructured":"Asano, T. et al. X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19. Sci. Immunol. 6, 62 (2021).","journal-title":"Sci. Immunol."},{"key":"2429_CR2","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1007\/s10875-024-01660-6","volume":"44","author":"C David","year":"2024","unstructured":"David, C. et al. Interface gain-of-function mutations in TLR7 cause systemic and neuro-inflammatory disease. J. Clin. Immunol. 44, 60 (2024).","journal-title":"J. Clin. Immunol."},{"key":"2429_CR3","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1038\/s41586-022-04642-z","volume":"605","author":"GJ Brown","year":"2022","unstructured":"Brown, G. J. et al. TLR7 gain-of-function genetic variation causes human lupus. Nature 605, 349\u2013356 (2022).","journal-title":"Nature"},{"key":"2429_CR4","doi-asserted-by":"publisher","first-page":"2450","DOI":"10.1182\/blood.2020009620","volume":"137","author":"J Aluri","year":"2021","unstructured":"Aluri, J. et al. Immunodeficiency and bone marrow failure with mosaic and germline TLR8 gain of function. Blood 137, 2450\u20132462 (2021).","journal-title":"Blood"},{"key":"2429_CR5","doi-asserted-by":"publisher","first-page":"1529","DOI":"10.1126\/science.1093616","volume":"303","author":"SS Diebold","year":"2004","unstructured":"Diebold, S. S. et al. Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science 303, 1529\u20131531 (2004).","journal-title":"Science"},{"key":"2429_CR6","doi-asserted-by":"publisher","first-page":"1526","DOI":"10.1126\/science.1093620","volume":"303","author":"F Heil","year":"2004","unstructured":"Heil, F. et al. Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8. Science 303, 1526\u20131529 (2004).","journal-title":"Science"},{"key":"2429_CR7","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1038\/nm1191","volume":"11","author":"V Hornung","year":"2005","unstructured":"Hornung, V. et al. Sequence-specific potent induction of IFN-alpha by short interfering RNA in plasmacytoid dendritic cells through TLR7. Nat. Med. 11, 263\u2013270 (2005).","journal-title":"Nat. Med."},{"key":"2429_CR8","doi-asserted-by":"publisher","first-page":"1426","DOI":"10.1126\/science.1229159","volume":"339","author":"H Tanji","year":"2013","unstructured":"Tanji, H., Ohto, U., Shibata, T., Miyake, K. & Shimizu, T. Structural reorganization of the Toll-like receptor 8 dimer induced by agonistic ligands. Science 339, 1426\u20131429 (2013).","journal-title":"Science"},{"key":"2429_CR9","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1038\/nsmb.2943","volume":"22","author":"H Tanji","year":"2015","unstructured":"Tanji, H. et al. Toll-like receptor 8 senses degradation products of single-stranded RNA. Nat. Struct. Mol. Biol. 22, 109\u2013115 (2015).","journal-title":"Nat. Struct. Mol. Biol."},{"key":"2429_CR10","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1016\/j.immuni.2016.09.011","volume":"45","author":"Z Zhang","year":"2016","unstructured":"Zhang, Z. et al. Structural analysis reveals that Toll-like receptor 7 is a dual receptor for guanosine and single-stranded RNA. Immunity 45, 737\u2013748 (2016).","journal-title":"Immunity"},{"key":"2429_CR11","doi-asserted-by":"publisher","first-page":"3371","DOI":"10.1016\/j.celrep.2018.11.081","volume":"25","author":"Z Zhang","year":"2018","unstructured":"Zhang, Z. et al. Structural analyses of Toll-like receptor 7 reveal detailed RNA sequence specificity and recognition mechanism of agonistic ligands. Cell Rep. 25, 3371\u20133381 (2018).","journal-title":"Cell Rep."},{"key":"2429_CR12","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1093\/intimm\/dxv062","volume":"28","author":"T Shibata","year":"2016","unstructured":"Shibata, T. et al. Guanosine and its modified derivatives are endogenous ligands for TLR7. Int. Immunol. 28, 211\u2013222 (2016).","journal-title":"Int. Immunol"},{"key":"2429_CR13","doi-asserted-by":"publisher","first-page":"1264","DOI":"10.1016\/j.cell.2019.11.001","volume":"179","author":"W Greulich","year":"2019","unstructured":"Greulich, W. et al. TLR8 is a sensor of RNase T2 degradation products. Cell 179, 1264\u20131275 (2019).","journal-title":"Cell"},{"key":"2429_CR14","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1016\/j.immuni.2020.03.009","volume":"52","author":"T Ostendorf","year":"2020","unstructured":"Ostendorf, T. et al. Immune sensing of synthetic, bacterial, and protozoan RNA by Toll-like receptor 8 requires coordinated processing by RNase T2 and RNase 2. Immunity 52, 591\u2013605 (2020).","journal-title":"Immunity"},{"key":"2429_CR15","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/j.immuni.2005.06.008","volume":"23","author":"K Kariko","year":"2005","unstructured":"Kariko, K., Buckstein, M., Ni, H. & Weissman, D. Suppression of RNA recognition by Toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA. Immunity 23, 165\u2013175 (2005).","journal-title":"Immunity"},{"key":"2429_CR16","doi-asserted-by":"publisher","first-page":"1663","DOI":"10.1038\/sj.mt.6300240","volume":"15","author":"M Robbins","year":"2007","unstructured":"Robbins, M. et al. 2\u2019-O-methyl-modified RNAs act as TLR7 antagonists. Mol. Ther. 15, 1663\u20131669 (2007).","journal-title":"Mol. Ther."},{"key":"2429_CR17","doi-asserted-by":"publisher","first-page":"7884","DOI":"10.1093\/nar\/gkw482","volume":"44","author":"N Krogh","year":"2016","unstructured":"Krogh, N. et al. Profiling of 2\u2019-O-Me in human rRNA reveals a subset of fractionally modified positions and provides evidence for ribosome heterogeneity. Nucleic Acids Res. 44, 7884\u20137895 (2016).","journal-title":"Nucleic Acids Res."},{"key":"2429_CR18","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1084\/jem.20111075","volume":"209","author":"S Jockel","year":"2012","unstructured":"Jockel, S. et al. The 2\u2019-O-methylation status of a single guanosine controls transfer RNA-mediated Toll-like receptor 7 activation or inhibition. J. Exp. Med. 209, 235\u2013241 (2012).","journal-title":"J. Exp. Med."},{"key":"2429_CR19","doi-asserted-by":"publisher","first-page":"8164","DOI":"10.4049\/jimmunol.177.11.8164","volume":"177","author":"KK Gorden","year":"2006","unstructured":"Gorden, K. K. et al. Oligodeoxynucleotides differentially modulate activation of TLR7 and TLR8 by imidazoquinolines. J. Immunol. 177, 8164\u20138170 (2006).","journal-title":"J. Immunol."},{"key":"2429_CR20","doi-asserted-by":"publisher","first-page":"1815","DOI":"10.1002\/eji.200535806","volume":"36","author":"M Jurk","year":"2006","unstructured":"Jurk, M. et al. Modulating responsiveness of human TLR7 and 8 to small molecule ligands with T-rich phosphorothiate oligodeoxynucleotides. Eur. J. Immunol. 36, 1815\u20131826 (2006).","journal-title":"Eur. J. Immunol."},{"key":"2429_CR21","first-page":"7052","volume":"48","author":"AS Alharbi","year":"2020","unstructured":"Alharbi, A. S. et al. Rational design of antisense oligonucleotides modulating the activity of TLR7\/8 agonists. Nucleic Acids Res. 48, 7052\u20137065 (2020).","journal-title":"Nucleic Acids Res."},{"key":"2429_CR22","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1124\/jpet.120.000275","volume":"376","author":"J Vlach","year":"2021","unstructured":"Vlach, J. et al. Discovery of M5049: a novel selective Toll-like receptor 7\/8 inhibitor for treatment of autoimmunity. J. Pharmacol. Exp. Ther. 376, 397\u2013409 (2021).","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"2429_CR23","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-017-0415-3","volume":"9","author":"WR Swindell","year":"2017","unstructured":"Swindell, W. R. et al. Imiquimod has strain-dependent effects in mice and does not uniquely model human psoriasis. Genome Med. 9, 24 (2017).","journal-title":"Genome Med."},{"key":"2429_CR24","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19025-z","volume":"11","author":"S Tojo","year":"2020","unstructured":"Tojo, S. et al. Structural analysis reveals TLR7 dynamics underlying antagonism. Nat. Commun. 11, 5204 (2020).","journal-title":"Nat. Commun."},{"key":"2429_CR25","doi-asserted-by":"publisher","first-page":"1305","DOI":"10.1038\/s12276-023-00999-x","volume":"55","author":"J Lee","year":"2023","unstructured":"Lee, J., Woodruff, M. C., Kim, E. H. & Nam, J.-H. Knife\u2019s edge: Balancing immunogenicity and reactogenicity in mRNA vaccines. Exp. Mol. Med. 55, 1305\u20131313 (2023).","journal-title":"Exp. Mol. Med."},{"key":"2429_CR26","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1016\/j.ard.2025.01.011","volume":"84","author":"Y Zeng","year":"2025","unstructured":"Zeng, Y. et al. Somatic gain-of-function mutation in TLR7 causes early-onset systemic lupus erythematosus. Ann. Rheum. Dis. 84, 442\u2013450 (2025).","journal-title":"Ann. Rheum. Dis."},{"key":"2429_CR27","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1038\/nchembio.2518","volume":"14","author":"S Zhang","year":"2017","unstructured":"Zhang, S. et al. Small-molecule inhibition of TLR8 through stabilization of its resting state. Nat. Chem. Biol. 14, 58\u201364 (2017).","journal-title":"Nat. Chem. Biol."},{"key":"2429_CR28","doi-asserted-by":"publisher","first-page":"1054","DOI":"10.1021\/acsmedchemlett.3c00136","volume":"14","author":"P Alper","year":"2023","unstructured":"Alper, P. et al. Discovery of the TLR7\/8 antagonist MHV370 for treatment of systemic autoimmune diseases. ACS Med. Chem. Lett. 14, 1054\u20131062 (2023).","journal-title":"ACS Med. Chem. Lett."},{"key":"2429_CR29","doi-asserted-by":"publisher","first-page":"E1625","DOI":"10.1073\/pnas.1519292113","volume":"113","author":"M Falaleeva","year":"2016","unstructured":"Falaleeva, M. et al. Dual function of C\/D box small nucleolar RNAs in rRNA modification and alternative pre-mRNA splicing. Proc. Natl Acad. Sci. USA 113, E1625\u2013E1634 (2016).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2429_CR30","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1007\/978-1-0716-1374-0_11","volume":"2298","author":"BA Elliott","year":"2021","unstructured":"Elliott, B. A. & Holley, C. L. Assessing 2\u2019-O-methylation of mRNA using quantitative PCR. Methods Mol. Biol. 2298, 171\u2013184 (2021).","journal-title":"Methods Mol. Biol."},{"key":"2429_CR31","doi-asserted-by":"publisher","first-page":"117","DOI":"10.3390\/genes10020117","volume":"10","author":"DG Dimitrova","year":"2019","unstructured":"Dimitrova, D. G., Teysset, L. & Carr\u00e9, C. RNA 2\u2019-O-methylation (Nm) modification in human diseases. Genes 10, 117 (2019).","journal-title":"Genes"},{"key":"2429_CR32","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.clim.2016.09.015","volume":"174","author":"DM Balak","year":"2017","unstructured":"Balak, D. M. et al. IMO-8400, a Toll-like receptor 7, 8, and 9 antagonist, demonstrates clinical activity in a phase 2a, randomized, placebo-controlled trial in patients with moderate-to-severe plaque psoriasis. Clin. Immunol. 174, 63\u201372 (2017).","journal-title":"Clin. Immunol"},{"key":"2429_CR33","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1093\/nar\/gku1343","volume":"43","author":"ST Sarvestani","year":"2015","unstructured":"Sarvestani, S. T. et al. Sequence-dependent off-target inhibition of TLR7\/8 sensing by synthetic microRNA inhibitors. Nucleic Acids Res. 43, 1177\u20131188 (2015).","journal-title":"Nucleic Acids Res."},{"key":"2429_CR34","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1038\/nature12306","volume":"498","author":"A Ablasser","year":"2013","unstructured":"Ablasser, A. et al. cGAS produces a 2\u2019-5\u2019-linked cyclic dinucleotide second messenger that activates STING. Nature 498, 380\u2013384 (2013).","journal-title":"Nature"},{"key":"2429_CR35","doi-asserted-by":"publisher","first-page":"2117","DOI":"10.4049\/jimmunol.180.4.2117","volume":"180","author":"MP Gantier","year":"2008","unstructured":"Gantier, M. P. et al. TLR7 is involved in sequence-specific sensing of single-stranded RNAs in human macrophages. J. Immunol. 180, 2117\u20132124 (2008).","journal-title":"J. Immunol."},{"key":"2429_CR36","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/1471-2172-2-11","volume":"2","author":"DA Hume","year":"2001","unstructured":"Hume, D. A. et al. Macrophages exposed continuously to lipopolysaccharide and other agonists that act via toll-like receptors exhibit a sustained and additive activation state. BMC Immunol 2, 11 (2001).","journal-title":"BMC Immunol"},{"key":"2429_CR37","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1038\/mt.2010.4","volume":"18","author":"MP Gantier","year":"2010","unstructured":"Gantier, M. P. et al. Rational design of immunostimulatory siRNAs. Mol. Ther. 18, 785\u2013795 (2010).","journal-title":"Mol. Ther."},{"key":"2429_CR38","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1007\/978-1-4939-3335-8_5","volume":"1390","author":"J Ferrand","year":"2016","unstructured":"Ferrand, J. & Gantier, M. P. Assessing the inhibitory activity of oligonucleotides on TLR7 sensing. Methods Mol. Biol. 1390, 79\u201390 (2016).","journal-title":"Methods Mol. Biol."},{"key":"2429_CR39","doi-asserted-by":"publisher","first-page":"6592","DOI":"10.4049\/jimmunol.174.11.6592","volume":"174","author":"SH Naik","year":"2005","unstructured":"Naik, S. H. et al. Cutting edge: generation of splenic CD8+ and CD8-dendritic cell equivalents in Fms-like tyrosine kinase 3 ligand bone marrow cultures. J. Immunol. 174, 6592\u20136597 (2005).","journal-title":"J. Immunol"},{"key":"2429_CR40","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1007\/978-1-60761-588-0_2","volume":"623","author":"MP Gantier","year":"2010","unstructured":"Gantier, M. P. & Williams, B. R. Monitoring innate immune recruitment by siRNAs in mammalian cells. Methods Mol. Biol. 623, 21\u201333 (2010).","journal-title":"Methods Mol. Biol."},{"key":"2429_CR41","doi-asserted-by":"publisher","first-page":"2245","DOI":"10.1007\/s00125-019-04988-6","volume":"62","author":"K Joshi","year":"2019","unstructured":"Joshi, K. et al. Induced pluripotent stem cell macrophages present antigen to proinsulin-specific T cell receptors from donor-matched islet-infiltrating T cells in type 1 diabetes. Diabetologia 62, 2245\u20132251 (2019).","journal-title":"Diabetologia"},{"key":"2429_CR42","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1016\/j.immuni.2018.04.011","volume":"48","author":"K Pelka","year":"2018","unstructured":"Pelka, K. et al. The chaperone UNC93B1 regulates Toll-like receptor stability independently of endosomal TLR transport. Immunity 48, 911\u2013922 (2018).","journal-title":"Immunity"},{"key":"2429_CR43","doi-asserted-by":"publisher","first-page":"e157","DOI":"10.1093\/nar\/gks698","volume":"40","author":"ZW Dong","year":"2012","unstructured":"Dong, Z. W. et al. RTL-P: a sensitive approach for detecting sites of 2\u2019-O-methylation in RNA molecules. Nucleic Acids Res. 40, e157 (2012).","journal-title":"Nucleic Acids Res."}],"container-title":["Nature Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41590-026-02429-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41590-026-02429-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41590-026-02429-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T17:02:31Z","timestamp":1775062951000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41590-026-02429-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,10]]},"references-count":43,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["2429"],"URL":"https:\/\/doi.org\/10.1038\/s41590-026-02429-2","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.07.25.605091","asserted-by":"object"}]},"ISSN":["1529-2908","1529-2916"],"issn-type":[{"value":"1529-2908","type":"print"},{"value":"1529-2916","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,10]]},"assertion":[{"value":"6 June 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 February 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"O.F.L., D.S.W. and M.S. are employees of Noxopharm and Pharmorage. M.P.G. and B.C.\u2019s groups receive funding from Noxopharm to study the activity of oligonucleotides on TLR7\/8. M.P.G. receives consulting and advisory fees from Noxopharm. M.P.G. does not personally own shares and\/or equity in Noxopharm. M.P.G., O.F.L., D.S.W., M.S. and S.S. are named inventors of a patent relating to the trimer oligonucleotide technology developed herein (WO2024077351). O.F.L. owns shares and\/or equity in Noxopharm. The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}