An unexpected role for RNA-sensing toll-like receptors in a murine model of DNA accrual

Clinical and Experimental Rheumatology

Volumn 33, Issue , 2015, Pages 70-73

  Pawaria, Sudesh ^a   Moody, Krishna L ^a,b   Busto, Patricia ^a   Nündel, Kerstin ^a   Baum, Rebecca ^a   Sharma, Shruti ^a   Gravallese, Ellen M ^a   Fitzgerald, Katherine A ^a   Marshak Rothstein, Ann ^a  

^a UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL   (United States)

^b BOSTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Anti nuclear antibody; Arthritis; Autoantibody; Bifunctional antibody; DNaseII; Extramedullary haematopoiesis; Splenomegaly; STING; TLR7; TLR9

Indexed keywords

ALPHA BETA INTERFERON RECEPTOR; ANTINUCLEAR ANTIBODY; AUTOANTIBODY; CHAPERONE; DEOXYRIBONUCLEASE II; DOUBLE STRANDED DNA; DOUBLE STRANDED DNA ANTIBODY; PROTEIN UNC93B1; RHEUMATOID FACTOR; TOLL LIKE RECEPTOR; TOLL LIKE RECEPTOR 7; TOLL LIKE RECEPTOR 9; UNCLASSIFIED DRUG; CARRIER PROTEIN; DEOXYRIBONUCLEASE; DNA; IFNAR1 PROTEIN, MOUSE; LIGAND; MEMBRANE PROTEIN; RNA; TLR7 PROTEIN, MOUSE; TLR9 PROTEIN, MOUSE; UNC93B1 PROTEIN, MOUSE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIBODY PRODUCTION; ARTHRITIS; ARTICLE; AUTOIMMUNITY; B LYMPHOCYTE; CYTOSOL; ENDOSOME; EXTRAMEDULLARY HEMATOPOIESIS; KNOCKOUT MOUSE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; SPLENOMEGALY; SYSTEMIC DISEASE; SYSTEMIC LUPUS ERYTHEMATOSUS; ANIMAL; DEFICIENCY; GENETICS; GENOTYPE; IMMUNOLOGY; METABOLISM; PHENOTYPE; SIGNAL TRANSDUCTION;

ANIMALS; ARTHRITIS; AUTOANTIBODIES; AUTOIMMUNITY; DNA; ENDODEOXYRIBONUCLEASES; ENDOSOMES; GENOTYPE; HEMATOPOIESIS, EXTRAMEDULLARY; LIGANDS; MEMBRANE GLYCOPROTEINS; MEMBRANE TRANSPORT PROTEINS; MICE, KNOCKOUT; PHENOTYPE; RECEPTOR, INTERFERON ALPHA-BETA; RNA; SIGNAL TRANSDUCTION; SPLENOMEGALY; TOLL-LIKE RECEPTOR 7; TOLL-LIKE RECEPTOR 9; TOLL-LIKE RECEPTORS;

EID: 84953343261     PISSN: 0392856X     EISSN: 1593098X     Source Type: Journal    
DOI: None     Document Type: Article

References (29)

1. MEDZHITOV R, PRESTON-HURLBURT P, JANEWAY CA, Jr.: A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 1997; 388: 394-7.
2. LEADBETTER EA, RIFKIN IR, HOHLBAUM AH, BEAUDETTE B, SHLOMCHIK MJ, MARSHAK-ROTHSTEIN A: Chromatin-IgG complexes activate autoreactive B cells by dual engagement of sIgM and Toll-like receptors. Nature 2002; 416: 603-7.
3. LAU CM, BROUGHTON C, TABOR AS et al.: RNA-associated autoantigens activate B cells by combined BCR/Toll-like receptor 7 engagement. J Exp Med 2005; 202: 1171-7.
4. TEICHMANN LL, SCHENTEN D, MEDZHITOV R, KASHGARIAN M, SHLOMCHIK MJ: Signals via the adaptor MyD88 in B cells and DCs make distinct and synergistic contributions to immune activation and tissue damage in lupus. Immunity 2013; 38: 528-40.
5. JACKSON SW, SCHARPING NE, KOLHATKAR NS et al.: Opposing impact of B cell-intrinsic TLR7 and TLR9 signals on autoantibody repertoire and systemic inflammation. J Immunol 2014; 192: 4525-32.
6. CHRISTENSEN SR, SHUPE J, NICKERSON K, KASHGARIAN M, FLAVELL RA, SHLOMCHIK MJ: Toll-like receptor 7 and TLR9 dictate autoantibody specificity and have opposing inflammatory and regulatory roles in a murine model of lupus. Immunity 2006: 25: 417-28.
7. CHAN OT, HANNUM LG, HABERMAN AM, MADAIO MP, SHLOMCHIK MJ: A novel mouse with B cells but lacking serum antibody reveals an antibody-independent role for B cells in murine lupus. J Exp Med 1999; 189: 1639-48.
8. SHARMA S, FitzGERALD KA: Innate immune sensing of DNA. PLoS Pathog 2011; 7: e1001310.
9. SUN L, WU J, DU F, CHEN X, CHEN ZJ: Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science 2013; 339: 786-91.
10. UNTERHOLZNER L, KEATING SE, BARAN M et al.: IFI16 is an innate immune sensor for intracellular DNA. Nat Immunol 2010; 11: 997-1004.
11. HORNUNG V, ABLASSER A, CHARREL-DENNIS M et al.: AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC. Nature 2009; 458: 514-8.
12. SETH RB, SUN L, EA CK, CHEN ZJ: Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3. Cell 2005; 122: 669-82.
13. CROW YJ, HAYWARD BE, PARMAR R et al.: Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 cause Aicardi-Goutieres syndrome at the AGS1 locus. Nat Genet 2006; 38: 917-20.
14. CROW YJ, REHWINKEL J: Aicardi-Goutieres syndrome and related phenotypes: linking nucleic acid metabolism with autoimmunity. Hum Mol Genet 2009; 18: R130-6.
15. LIU Y, JESUS AA, MARRERO B et al.: Activated STING in a vascular and pulmonary syndrome. N Engl J Med 2014; 371: 507-18.
16. JEREMIAH N, NEVEN B, GENTILI M et al.: Inherited STING-activating mutation underlies a familial inflammatory syndrome with lupus-like manifestations. J Clin Invest 2014; 124: 5516-20.
17. NAGATA S: Autoimmune diseases caused by defects in clearing dead cells and nuclei expelled from erythroid precursors. Immunol Rev 2007; 220: 237-50.
18. LAN YY, LONDONO D, BOULEY R, ROONEY MS, HACOHEN N: Dnase2a deficiency uncovers lysosomal clearance of damaged nuclear DNA via autophagy. Cell Rep 2014; 9: 180-92.
19. YOSHIDA H, OKABE Y, KAWANE K, FUKUYAMA H, NAGATA S: Lethal anemia caused by interferon-beta produced in mouse embryos carrying undigested DNA. Nat Immunol 2005; 6: 49-56.
20. AHN J, GUTMAN D, SAIJO S, BARBER GN: STING manifests self DNA-dependent inflammatory disease. Proc Natl Acad Sci USA 2012; 109: 19386-91.
21. KAWANE K, OHTANI M, MIWA K et al.: Chronic polyarthritis caused by mammalian DNA that escapes from degradation in macrophages. Nature 2006; 443: 998-1002.
22. BAUM R, SHARMA S, CARPENTER S et al.: Cutting Edge: AIM2 and Endosomal TLRs Differentially Regulate Arthritis and Autoantibody Production in DNase II-Deficient Mice. J Immunol 2015; 194: 873-7.
23. ROSSOL M, PIERER M, ARNOLD S et al.: Homozygosity for DNASE2 single nucleotide polymorphisms in the 5'-regulatory region is associated with rheumatoid arthritis. Ann Rheum Dis 2009; 68: 1498-503.
24. SHIN HD, PARK BL, CHEONG HS, LEE HS, JUN JB, BAE SC: DNase II polymorphisms associated with risk of renal disorder among systemic lupus erythematosus patients. J Hum Genet 2005; 50: 107-11.
25. PAWARIA S, MOODY K, BUSTO P et al.: Cutting Edge: DNase II Deficiency Prevents Activation of Autoreactive B Cells by Double-Stranded DNA Endogenous Ligands. J Immunol 2015; 194: 1403-7.
26. MARSHAK-ROTHSTEIN A: Toll-like receptors in systemic autoimmune disease. Nat Rev Immunol 2006; 6: 823-35.
27. VIGLIANTI GA, LAU CM, HANLEY TM, MIKO BA, SHLOMCHIK MJ, MARSHAK-ROTHSTEIN A: Activation of autoreactive B cells by CpG dsDNA. Immunity 2003; 19: 837-47.
28. CHAN MP, ONJI M, FUKUI R et al.: DNase II-dependent DNA digestion is required for DNA sensing by TLR9. Nat Commun 2015; 6: 5853.
29. GREEN NM, LAWS A, KIEFER K et al.: Murine B cell response to TLR7 ligands depends on an IFN-beta feedback loop. J Immunol 2009; 183: 1569-76.