Pawaria, SudeshMoody, Krishna L.Busto, PatriciaNundel, KerstinBaum, RebeccaSharma, ShrutieGravallese, Ellen M.Fitzgerald, Katherine AMarshak-Rothstein, Ann2022-08-232022-08-232015-07-012016-05-09Clin Exp Rheumatol. 2015 Jul-Aug;33(4 Suppl 92):S70-3. Epub 2015 Oct 12. <a href="http://www.clinexprheumatol.org/abstract.asp?a=9883">Link to article on publisher's website</a>0392-856X (Linking)26457825https://hdl.handle.net/20.500.14038/30685OBJECTIVES: The goal of this study was to determine whether endosomal Toll-like receptors (TLRs) contribute to the clinical manifestation of systemic autoimmunity exhibited by mice that lack the lysosomal nuclease DNaseII. METHODS: DNaseII/IFNaR double deficient mice were intercrossed with Unc93b13d/3d mice to generate DNaseII-/-mice with non-functional endosomal TLRs. The resulting triple deficient mice were evaluated for arthritis, autoantibody production, splenomegaly, and extramedullary haematopoiesis. B cells from both strains were evaluated for their capacity to respond to endogenous DNA by using small oligonucleotide based TLR9D ligands and a novel class of bifunctional anti-DNA antibodies. RESULTS: Mice that fail to express DNaseII, IFNaR, and Unc93b1 still develop arthritis but do not make autoantibodies, develop splenomegaly, or exhibit extramedullary haematopoiesis. DNaseII-/- IFNaR-/- B cells can respond to synthetic ODNs, but not to endogenous dsDNA. CONCLUSIONS: RNA-reactive TLRs, presumably TLR7, are required for autoantibody production, splenomegaly, and extramedullary haematopoiesis in the DNaseII-/- model of systemic autoimmunity.en-USAnimalsArthritisAutoantibodies*AutoimmunityDNAEndodeoxyribonucleasesEndosomesGenotypeHematopoiesis, ExtramedullaryLigandsMembrane GlycoproteinsMembrane Transport ProteinsMice, KnockoutPhenotypeRNAReceptor, Interferon alpha-betaSignal TransductionSplenomegalyToll-Like Receptor 7Toll-Like Receptor 9Toll-Like ReceptorsImmunityRheumatologyJournal Articlehttps://escholarship.umassmed.edu/faculty_pubs/9638575183faculty_pubs/963