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dc.contributor.authorBaum, Rebecca
dc.contributor.authorSharma, Shrutie
dc.contributor.authorCarpenter, Susan
dc.contributor.authorLi, Quan-Zhen
dc.contributor.authorBusto, Patricia
dc.contributor.authorFitzgerald, Katherine A.
dc.contributor.authorMarshak-Rothstein, Ann
dc.contributor.authorGravallese, Ellen M.
dc.date2022-08-11T08:10:51.000
dc.date.accessioned2022-08-23T17:22:28Z
dc.date.available2022-08-23T17:22:28Z
dc.date.issued2015-02-01
dc.date.submitted2015-02-23
dc.identifier.citationJ Immunol. 2015 Feb 1;194(3):873-7. doi: 10.4049/jimmunol.1402573. Epub 2014 Dec 29. <a href="http://dx.doi.org/10.4049/jimmunol.1402573">Link to article on publisher's site</a>
dc.identifier.issn0022-1767 (Linking)
dc.identifier.doi10.4049/jimmunol.1402573
dc.identifier.pmid25548216
dc.identifier.urihttp://hdl.handle.net/20.500.14038/48752
dc.description.abstractInnate 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(-/-) type I IFN receptor [Ifnar](-/-)) to understand the role of pattern recognition receptor-sensing 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(-/-) Ifnar(-/-) 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-sensing pathways in disease manifestations.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=25548216&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.4049/jimmunol.1402573
dc.subjectImmune System Diseases
dc.subjectImmunity
dc.subjectMusculoskeletal Diseases
dc.subjectNucleic Acids, Nucleotides, and Nucleosides
dc.subjectRheumatology
dc.titleCutting Edge: AIM2 and Endosomal TLRs Differentially Regulate Arthritis and Autoantibody Production in DNase II-Deficient Mice
dc.typeJournal Article
dc.source.journaltitleJournal of immunology (Baltimore, Md. : 1950)
dc.source.volume194
dc.source.issue3
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/rheumatology_pubs/5
dc.legacy.embargo2000-01-01T00:00:00-08:00
dc.identifier.contextkey6706281
html.description.abstract<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(-/-) type I IFN receptor [Ifnar](-/-)) to understand the role of pattern recognition receptor-sensing 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(-/-) Ifnar(-/-) 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-sensing pathways in disease manifestations.</p>
dc.identifier.submissionpathrheumatology_pubs/5
dc.contributor.departmentDepartment of Medicine, Division of Infectious Diseases and Immunology
dc.contributor.departmentDepartment of Medicine, Division of Rheumatology
dc.source.pages873-7


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