{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T15:44:57Z","timestamp":1790783097193,"version":"4.1.0"},"reference-count":18,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2015,2,1]],"date-time":"2015-02-01T00:00:00Z","timestamp":1422748800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Innate immune pattern recognition receptors sense nucleic acids from microbes and orchestrate cytokine production to resolve infection. Inappropriate recognition of host nucleic acids also results in autoimmune disease. In this study, we use a model of inflammation resulting from accrual of self DNA (DNase II\u2212\/\u2212 type I IFN receptor [Ifnar]\u2212\/\u2212) to understand the role of pattern recognition receptor\u2013sensing pathways in arthritis and autoantibody production. Using triple knockout (TKO) mice deficient in DNase II\/IFNaR together with deficiency in either stimulator of IFN genes (STING) or absent in melanoma 2 (AIM2), we reveal central roles for the STING and AIM2 pathways in arthritis. AIM2 TKO mice show limited inflammasome activation and, similar to STING TKO mice, have reduced inflammation in joints. Surprisingly, autoantibody production is maintained in AIM2 and STING TKO mice, whereas DNase II\u2212\/\u2212 Ifnar\u2212\/\u2212 mice also deficient in Unc93b, a chaperone required for TLR7\/9 endosomal localization, fail to produce autoantibodies to nucleic acids. Collectively, these data support distinct roles for cytosolic and endosomal nucleic acid\u2013sensing pathways in disease manifestations.<\/jats:p>","DOI":"10.4049\/jimmunol.1402573","type":"journal-article","created":{"date-parts":[[2014,12,30]],"date-time":"2014-12-30T08:27:26Z","timestamp":1419928046000},"page":"873-877","source":"Crossref","is-referenced-by-count":104,"title":["Cutting Edge: AIM2 and Endosomal TLRs Differentially Regulate Arthritis and Autoantibody Production in DNase II\u2013Deficient Mice"],"prefix":"10.1093","volume":"194","author":[{"given":"Rebecca","family":"Baum","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, University of Massachusetts Medical School , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shruti","family":"Sharma","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, University of Massachusetts Medical School , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Carpenter","sequence":"additional","affiliation":[{"name":"Diabetes Center, Department of Microbiology and Immunology, University of California San Francisco , San Francisco, CA 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan-Zhen","family":"Li","sequence":"additional","affiliation":[{"name":"Microarray Core Facility, Department of Immunology, University of Texas Southwestern Medical Center , Dallas, TX 75235"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Busto","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, University of Massachusetts Medical School , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine A","family":"Fitzgerald","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Marshak-Rothstein","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, University of Massachusetts Medical School , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen M","family":"Gravallese","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, University of Massachusetts Medical School , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,2,1]]},"reference":[{"key":"2025030704565606600_r1","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1038\/nm1590","article-title":"TLR-dependent and TLR-independent pathways of type I interferon induction in systemic autoimmunity","volume":"13","author":"Baccala","year":"2007","journal-title":"Nat. Med."},{"key":"2025030704565606600_r2","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1056\/NEJMoa1312625","article-title":"Activated STING in a vascular and pulmonary syndrome","volume":"371","author":"Liu","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"2025030704565606600_r3","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/ni1146","article-title":"Lethal anemia caused by interferon-\u03b2 produced in mouse embryos carrying undigested DNA","volume":"6","author":"Yoshida","year":"2005","journal-title":"Nat. Immunol."},{"key":"2025030704565606600_r4","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1038\/nature05245","article-title":"Chronic polyarthritis caused by mammalian DNA that escapes from degradation in macrophages","volume":"443","author":"Kawane","year":"2006","journal-title":"Nature"},{"key":"2025030704565606600_r5","doi-asserted-by":"crossref","first-page":"19432","DOI":"10.1073\/pnas.1010603107","article-title":"Cytokine-dependent but acquired immunity-independent arthritis caused by DNA escaped from degradation","volume":"107","author":"Kawane","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025030704565606600_r6","doi-asserted-by":"crossref","first-page":"19386","DOI":"10.1073\/pnas.1215006109","article-title":"STING manifests self DNA-dependent inflammatory disease","volume":"109","author":"Ahn","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025030704565606600_r7","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/ni.2237","article-title":"Regulation of inflammasome signaling","volume":"13","author":"Rathinam","year":"2012","journal-title":"Nat. Immunol."},{"key":"2025030704565606600_r8","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1038\/nature08476","article-title":"STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity","volume":"461","author":"Ishikawa","year":"2009","journal-title":"Nature"},{"key":"2025030704565606600_r9","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1038\/ni.1864","article-title":"The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses","volume":"11","author":"Rathinam","year":"2010","journal-title":"Nat. Immunol."},{"key":"2025030704565606600_r10","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1016\/S0002-9440(10)63016-7","article-title":"TRANCE\/RANKL knockout mice are protected from bone erosion in a serum transfer model of arthritis","volume":"159","author":"Pettit","year":"2001","journal-title":"Am. J. Pathol."},{"key":"2025030704565606600_r11","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/S1074-7613(00)80045-X","article-title":"From systemic T cell self-reactivity to organ-specific autoimmune disease via immunoglobulins","volume":"10","author":"Korganow","year":"1999","journal-title":"Immunity"},{"key":"2025030704565606600_r12","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1359\/jbmr.090320","article-title":"Osteoblast function is compromised at sites of focal bone erosion in inflammatory arthritis","volume":"24","author":"Walsh","year":"2009","journal-title":"J. Bone Miner. Res."},{"key":"2025030704565606600_r13","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1111\/j.1365-2249.2006.03251.x","article-title":"Protein array autoantibody profiles for insights into systemic lupus erythematosus and incomplete lupus syndromes","volume":"147","author":"Li","year":"2007","journal-title":"Clin. Exp. Immunol."},{"key":"2025030704565606600_r14","doi-asserted-by":"crossref","first-page":"4795","DOI":"10.1007\/s00018-013-1425-y","article-title":"IL-18 in inflammatory and autoimmune disease","volume":"70","author":"Sedimbi","year":"2013","journal-title":"Cell. Mol. Life Sci."},{"key":"2025030704565606600_r15","doi-asserted-by":"crossref","first-page":"R130","DOI":"10.1186\/gb-2009-10-11-r130","article-title":"BioGPS: an extensible and customizable portal for querying and organizing gene annotation resources","volume":"10","author":"Wu","year":"2009","journal-title":"Genome Biol."},{"key":"2025030704565606600_r16","doi-asserted-by":"crossref","first-page":"2517","DOI":"10.1002\/1529-0131(199912)42:12<2517::AID-ANR3>3.0.CO;2-W","article-title":"The arthritogenic T cell receptor and its ligand in a model of spontaneous arthritis","volume":"42","author":"Mangialaio","year":"1999","journal-title":"Arthritis Rheum."},{"key":"2025030704565606600_r17","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/j.cell.2008.06.032","article-title":"Trex1 prevents cell-intrinsic initiation of autoimmunity","volume":"134","author":"Stetson","year":"2008","journal-title":"Cell"},{"key":"2025030704565606600_r18","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1038\/ng1845","article-title":"Mutations in the gene encoding the 3\u2032-5\u2032 DNA exonuclease TREX1 cause Aicardi-Gouti\u00e8res syndrome at the AGS1 locus","volume":"38","author":"Crow","year":"2006","journal-title":"Nat. Genet."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/194\/3\/873\/62237185\/1402573.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/194\/3\/873\/62237185\/1402573.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T06:14:31Z","timestamp":1741328071000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/194\/3\/873\/7972885"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,2,1]]},"references-count":18,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2015,2,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1402573","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2015,2]]},"published":{"date-parts":[[2015,2,1]]}}}