Cutting Edge: AIM2 and Endosomal TLRs Differentially Regulate Arthritis and Autoantibody Production in DNase II-Deficient Mice. J Immunol. 2014 Dec 29. Rebecca Baum1, Shruti Sharma1, Susan Carpenter2, Quan-Zhen Li3, Patricia Busto1, Kate A Fitzgerald4, Ann Marshak-Rothstein1, Ellen M. Gravallese5. Author information 1Division of Rheumatology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605; 2Diabetes Center, Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA 94143; 3Microarray Core Facility, Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75235; and. 4Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605. 5Division of Rheumatology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605; Abstract 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. jimmunol.org/content/early/2014/12/28/jimmunol.1402573.long
Posted on: Thu, 15 Jan 2015 18:22:45 +0000
Trending Topics
Recently Viewed Topics
© 2015