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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2019,11,19]]},"abstract":"<jats:p>The activation of innate immune receptors by pathogen-associated molecular patterns (PAMPs) is central to host defense against infections. On the other hand, these receptors are also activated by immunogenic damage-associated molecular patterns (DAMPs), typically released from dying cells, and the activation can evoke chronic inflammatory or autoimmune disorders. One of the best known receptors involved in the immune pathogenesis is Toll-like receptor 7 (TLR7), which recognizes RNA with single-stranded structure. However, the causative DAMP RNA(s) in the pathogenesis has yet to be identified. Here, we first developed a chemical compound, termed KN69, that suppresses autoimmunity in several established mouse models. A subsequent search for KN69-binding partners led to the identification of U11 small nuclear RNA (U11snRNA) as a candidate DAMP RNA involved in TLR7-induced autoimmunity. We then showed that U11snRNA robustly activated the TLR7 pathway in vitro and induced arthritis disease in vivo. We also found a correlation between high serum level of U11snRNA and autoimmune diseases in human subjects and established mouse models. Finally, by revealing the structural basis for U11snRNA\u2019s ability to activate TLR7, we developed more potent TLR7 agonists and TLR7 antagonists, which may offer new therapeutic approaches for autoimmunity or other immune-driven diseases. Thus, our study has revealed a hitherto unknown immune function of U11snRNA, providing insight into TLR7-mediated autoimmunity and its potential for further therapeutic applications.<\/jats:p>","DOI":"10.1073\/pnas.1915326116","type":"journal-article","created":{"date-parts":[[2019,11,6]],"date-time":"2019-11-06T19:55:12Z","timestamp":1573070112000},"page":"23653-23661","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":22,"title":["Identification of U11snRNA as an endogenous agonist of TLR7-mediated immune pathogenesis"],"prefix":"10.1073","volume":"116","author":[{"given":"Hideo","family":"Negishi","sequence":"first","affiliation":[{"name":"Department of Molecular Immunology, Institute of Industrial Science, The University of Tokyo, 153-8505 Tokyo, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuyasu","family":"Endo","sequence":"additional","affiliation":[{"name":"Department of Molecular Immunology, Institute of Industrial Science, The University of Tokyo, 153-8505 Tokyo, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Nakajima","sequence":"additional","affiliation":[{"name":"Department of Molecular Immunology, Institute of Industrial Science, The University of Tokyo, 153-8505 Tokyo, Japan;"},{"name":"Department of Inflammology, Research Center for Advanced Science and Technology, The University of Tokyo, 153-0041 Tokyo, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuaki","family":"Nishiyama","sequence":"additional","affiliation":[{"name":"Tokyo New Drug Research Laboratories, Pharmaceutical Division, Kowa Company, Ltd., 189-0022 Higashimurayama, Tokyo, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichiro","family":"Tabunoki","sequence":"additional","affiliation":[{"name":"Tokyo New Drug Research Laboratories, Pharmaceutical Division, Kowa Company, Ltd., 189-0022 Higashimurayama, Tokyo, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junko","family":"Nishio","sequence":"additional","affiliation":[{"name":"Department of Molecular Immunology, Institute of Industrial Science, The University of Tokyo, 153-8505 Tokyo, Japan;"},{"name":"Department of Inflammology, Research Center for Advanced Science and Technology, The University of Tokyo, 153-0041 Tokyo, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryuji","family":"Koshiba","sequence":"additional","affiliation":[{"name":"Department of Molecular Immunology, Institute of Industrial Science, The University of Tokyo, 153-8505 Tokyo, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Matsuda","sequence":"additional","affiliation":[{"name":"Department of Molecular Immunology, Institute of Industrial Science, The University of Tokyo, 153-8505 Tokyo, 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Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6376-2841","authenticated-orcid":false,"given":"Takeshi","family":"Ichinohe","sequence":"additional","affiliation":[{"name":"Division of Viral Infection, Department of Infectious Disease Control, International Research Center for Infectious Diseases, Institute of Medical Science, The University of Tokyo, 108-8639 Tokyo, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunji","family":"Takemura","sequence":"additional","affiliation":[{"name":"Tokyo New Drug Research Laboratories, Pharmaceutical Division, Kowa Company, Ltd., 189-0022 Higashimurayama, Tokyo, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Ishiwata","sequence":"additional","affiliation":[{"name":"Tokyo New Drug Research Laboratories, Pharmaceutical Division, Kowa Company, Ltd., 189-0022 Higashimurayama, Tokyo, 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Lande ., Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Nature 449, 564\u2013569 (2007).","journal-title":"Nature"},{"key":"e_1_3_4_29_2","doi-asserted-by":"crossref","first-page":"D303","DOI":"10.1093\/nar\/gkx1030","article-title":"MODOMICS: A database of RNA modification pathways. 2017 update","volume":"46","author":"Boccaletto P.","year":"2018","unstructured":"P. Boccaletto ., MODOMICS: A database of RNA modification pathways. 2017 update. Nucleic Acids Res. 46, D303\u2013D307 (2018).","journal-title":"Nucleic Acids Res."},{"key":"e_1_3_4_30_2","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1038\/nature05228","article-title":"An early evolutionary origin for the minor spliceosome","volume":"443","author":"Russell A. G.","year":"2006","unstructured":"A. G. Russell, J. M. Charette, D. F. Spencer, M. W. Gray, An early evolutionary origin for the minor spliceosome. 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Pohar ., Phosphodiester backbone of the CpG motif within immunostimulatory oligodeoxynucleotides augments activation of Toll-like receptor 9. Sci. Rep. 7, 14598 (2017).","journal-title":"Sci. Rep."},{"key":"e_1_3_4_33_2","doi-asserted-by":"crossref","first-page":"828","DOI":"10.4161\/rna.20206","article-title":"RNA mediated Toll-like receptor stimulation in health and disease","volume":"9","author":"Dalpke A.","year":"2012","unstructured":"A. Dalpke, M. Helm, RNA mediated Toll-like receptor stimulation in health and disease. RNA Biol. 9, 828\u2013842 (2012).","journal-title":"RNA Biol."},{"key":"e_1_3_4_34_2","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1126\/science.aau1646","article-title":"RNA modifications modulate gene expression during development","volume":"361","author":"Frye M.","year":"2018","unstructured":"M. Frye, B. T. Harada, M. Behm, C. He, RNA modifications modulate gene expression during development. Science 361, 1346\u20131349 (2018).","journal-title":"Science"},{"key":"e_1_3_4_35_2","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.immuni.2005.06.008","article-title":"Suppression of RNA recognition by Toll-like receptors: The impact of nucleoside modification and the evolutionary origin of RNA","volume":"23","author":"Karik\u00f3 K.","year":"2005","unstructured":"K. Karik\u00f3, M. Buckstein, H. Ni, D. Weissman, 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":"e_1_3_4_36_2","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1084\/jem.20111075","article-title":"The 2\u2032-O-methylation status of a single guanosine controls transfer RNA-mediated Toll-like receptor 7 activation or inhibition","volume":"209","author":"J\u00f6ckel S.","year":"2012","unstructured":"S. J\u00f6ckel ., The 2\u2032-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":"e_1_3_4_37_2","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1159\/000375460","article-title":"2\u2032-O-methylation within bacterial RNA acts as suppressor of TLR7\/TLR8 activation in human innate immune cells","volume":"7","author":"Rimbach K.","year":"2015","unstructured":"K. Rimbach, S. Kaiser, M. Helm, A. H. Dalpke, T. Eigenbrod, 2\u2032-O-methylation within bacterial RNA acts as suppressor of TLR7\/TLR8 activation in human innate immune cells. J. Innate Immun. 7, 482\u2013493 (2015).","journal-title":"J. Innate Immun."},{"key":"e_1_3_4_38_2","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1261\/rna.030106.111","article-title":"Post-transcriptional modification of spliceosomal RNAs is normal in SMN-deficient cells","volume":"18","author":"Deryusheva S.","year":"2012","unstructured":"S. Deryusheva, M. Choleza, A. Barbarossa, J. G. Gall, R. Bordonn\u00e9, Post-transcriptional modification of spliceosomal RNAs is normal in SMN-deficient cells. RNA 18, 31\u201336 (2012).","journal-title":"RNA"},{"key":"e_1_3_4_39_2","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1017\/S1355838299991537","article-title":"A limited number of pseudouridine residues in the human atac spliceosomal UsnRNAs as compared to human major spliceosomal UsnRNAs","volume":"5","author":"Massenet S.","year":"1999","unstructured":"S. Massenet, C. Branlant, A limited number of pseudouridine residues in the human atac spliceosomal UsnRNAs as compared to human major spliceosomal UsnRNAs. RNA 5, 1495\u20131503 (1999).","journal-title":"RNA"},{"key":"e_1_3_4_40_2","doi-asserted-by":"crossref","first-page":"192","DOI":"10.4161\/rna.7.2.11207","article-title":"Spliceosomal snRNA modifications and their function","volume":"7","author":"Karijolich J.","year":"2010","unstructured":"J. Karijolich, Y. T. Yu, Spliceosomal snRNA modifications and their function. RNA Biol. 7, 192\u2013204 (2010).","journal-title":"RNA Biol."},{"key":"e_1_3_4_41_2","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1126\/science.1071059","article-title":"The danger model: A renewed sense of self","volume":"296","author":"Matzinger P.","year":"2002","unstructured":"P. Matzinger, The danger model: A renewed sense of self. Science 296, 301\u2013305 (2002).","journal-title":"Science"},{"key":"e_1_3_4_42_2","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1038\/nm.2861","article-title":"Ultraviolet radiation damages self noncoding RNA and is detected by TLR3","volume":"18","author":"Bernard J. J.","year":"2012","unstructured":"J. J. Bernard ., Ultraviolet radiation damages self noncoding RNA and is detected by TLR3. Nat. Med. 18, 1286\u20131290 (2012).","journal-title":"Nat. Med."},{"key":"e_1_3_4_43_2","doi-asserted-by":"crossref","first-page":"5041","DOI":"10.1093\/nar\/gkp525","article-title":"Activation of interferon regulatory factor-3 via Toll-like receptor 3 and immunomodulatory functions detected in A549 lung epithelial cells exposed to misplaced U1-snRNA","volume":"37","author":"Sadik C. D.","year":"2009","unstructured":"C. D. Sadik, M. Bachmann, J. Pfeilschifter, H. M\u00fchl, Activation of interferon regulatory factor-3 via Toll-like receptor 3 and immunomodulatory functions detected in A549 lung epithelial cells exposed to misplaced U1-snRNA. Nucleic Acids Res. 37, 5041\u20135056 (2009).","journal-title":"Nucleic Acids Res."},{"key":"e_1_3_4_44_2","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1002\/art.21566","article-title":"A murine model of mixed connective tissue disease induced with U1 small nuclear RNP autoantigen","volume":"54","author":"Greidinger E. L.","year":"2006","unstructured":"E. L. Greidinger ., A murine model of mixed connective tissue disease induced with U1 small nuclear RNP autoantigen. Arthritis Rheum. 54, 661\u2013669 (2006).","journal-title":"Arthritis Rheum."},{"key":"e_1_3_4_45_2","doi-asserted-by":"crossref","first-page":"12067","DOI":"10.1073\/pnas.0900971106","article-title":"5\u2032-triphosphate RNA requires base-paired structures to activate antiviral signaling via RIG-I","volume":"106","author":"Schmidt A.","year":"2009","unstructured":"A. Schmidt ., 5\u2032-triphosphate RNA requires base-paired structures to activate antiviral signaling via RIG-I. Proc. Natl. Acad. Sci. U.S.A. 106, 12067\u201312072 (2009).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"e_1_3_4_46_2","doi-asserted-by":"crossref","first-page":"8258","DOI":"10.1074\/jbc.M112.440883","article-title":"The human antimicrobial peptide LL-37, but not the mouse ortholog, mCRAMP, can stimulate signaling by poly(I:C) through a FPRL1-dependent pathway","volume":"288","author":"Singh D.","year":"2013","unstructured":"D. Singh, R. Qi, J. L. Jordan, L. San Mateo, C. C. Kao, The human antimicrobial peptide LL-37, but not the mouse ortholog, mCRAMP, can stimulate signaling by poly(I:C) through a FPRL1-dependent pathway. J. Biol. Chem. 288, 8258\u20138268 (2013).","journal-title":"J. Biol. Chem."},{"key":"e_1_3_4_47_2","doi-asserted-by":"crossref","first-page":"304","DOI":"10.3389\/fphar.2017.00304","article-title":"Anti-tumor activity of Toll-like receptor 7 agonists","volume":"8","author":"Chi H.","year":"2017","unstructured":"H. Chi ., Anti-tumor activity of Toll-like receptor 7 agonists. Front. Pharmacol. 8, 304 (2017).","journal-title":"Front. Pharmacol."},{"key":"e_1_3_4_48_2","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1038\/ni758","article-title":"Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway","volume":"3","author":"Hemmi H.","year":"2002","unstructured":"H. Hemmi ., Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway. Nat. Immunol. 3, 196\u2013200 (2002).","journal-title":"Nat. Immunol."},{"key":"e_1_3_4_49_2","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1038\/35047123","article-title":"A Toll-like receptor recognizes bacterial DNA","volume":"408","author":"Hemmi H.","year":"2000","unstructured":"H. Hemmi ., A Toll-like receptor recognizes bacterial DNA. 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