Neutrophils activate plasmacytoid dendritic cells by releasing self-DNA-peptide complexes in systemic lupus erythematosus

Science Translational Medicine

Volumn 3, Issue 73, 2011, Pages

  Lande, Roberto ^a,b,g   Ganguly, Dipyaman ^a,c   Facchinetti, Valeria ^a   Frasca, Loredana ^b   Conrad, Curdin ^a,g   Gregorio, Josh ^a,c   Meller, Stephan ^a   Chamilos, Georgios ^a   Sebasigari, Rosalie ^a   Riccieri, Valeria ^d   Bassett, Roland ^a   Amuro, Hideki ^e   Fukuhara, Shirou ^e   Ito, Tomoki ^e   Liu, Yong Jun ^a   Gilliet, Michel ^a,c,f,g  

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^b ISTITUTO SUPERIORE DI SANITÀ   (Italy)

^c UNIVERSITY OF TEXAS   (United States)

^d SAPIENZA UNIVERSITY OF ROME   (Italy)

^e KANSAI MEDICAL UNIVERSITY   (Japan)

^f University of Texas Health Science Center at Houston   (United States)

^g LAUSANNE UNIVERSITY HOSPITAL   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

AUTOANTIBODY; AUTOANTIGEN; DNA; DNA ANTIBODY; PEPTIDE DERIVATIVE; TOLL LIKE RECEPTOR 9; ANTIMICROBIAL PEPTIDE LL-37; ANTINUCLEAR ANTIBODY; CATHELICIDIN; CATHELICIDIN ANTIMICROBIAL PEPTIDE LL 37; PEPTIDE; TLR9 PROTEIN, HUMAN;

ANTIBODY PRODUCTION; ANTIGEN ANTIBODY REACTION; ARTICLE; B LYMPHOCYTE ACTIVATION; CELL INTERACTION; CONTROLLED STUDY; DNA PROTEIN COMPLEX; DNA SYNTHESIS; EXTRACELLULAR MATRIX; HUMAN; HUMAN CELL; IMMUNOPATHOGENESIS; IMMUNOSTIMULATION; INNATE IMMUNITY; LEUKOCYTE ACTIVATION; LEUKOCYTE FUNCTION; MAJOR CLINICAL STUDY; PLASMACYTOID DENDRITIC CELL; PRIORITY JOURNAL; PROTEIN SECRETION; SEROLOGY; SYSTEMIC LUPUS ERYTHEMATOSUS; ANTIGEN ANTIBODY COMPLEX; B LYMPHOCYTE; BLOOD; CASE CONTROL STUDY; DENDRITIC CELL; IMMUNOLOGY; LYMPHOCYTE ACTIVATION; METABOLISM; NEUTROPHIL;

ANTIBODIES, ANTINUCLEAR; ANTIGEN-ANTIBODY COMPLEX; AUTOANTIGENS; B-LYMPHOCYTES; CASE-CONTROL STUDIES; CATHELICIDINS; DENDRITIC CELLS; DNA; HUMANS; LUPUS ERYTHEMATOSUS, SYSTEMIC; LYMPHOCYTE ACTIVATION; NEUTROPHILS; PEPTIDES; TOLL-LIKE RECEPTOR 9;

EID: 79952468782     PISSN: 19466234     EISSN: 19466242     Source Type: Journal    
DOI: 10.1126/scitranslmed.3001180     Document Type: Article

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50. Acknowledgments: We thank S. Jung (Proteomics Core Pathway Discovery Facility, Baylor College of Medicine) for electrospray ionization mass spectrometric analyses and K. Ramirez (Flow Cytometry Core Facility, M. D. Anderson Cancer Center) for performing cell sorting. Funding: This work was funded by a grant from the M. D. Anderson Cancer Foundation and a PO1 grant from the National Cancer Institute (CA128913) to M.G. Author contributions: R.L. performed and analyzed most of the experiments in this study and participated in their design. D.G. performed microscopy studies of DNA particles. V.F. performed immunoblot experiments. L.F. performed the neutrophil stimulation experiments in Fig. 6. C.C. performed the DNA complexation assays described in Figs. 2 and 3 and helped with the statistical analyses. J.G. purified immune complexes by high-performance liquid chromatography. S.M. participated in the confocal microscopy experiments. G.C. participated in the DNA complexation experiments. R.S. participated in the measurement of autoantibodies by ELISA. V.R., H.A., S.F., and T. I. provided patient samples and data. R.B. helped with statistical analyses. Y.-J.L. provided critical suggestions and discussions throughout the study. M.G. conceived and supervised this study, was involved in the design and evaluation of all experiments, and wrote the manuscript with comments from co-authors. Competing interests: R.L. and M.G. hold a patent, "Inhibitors of LL-37 mediated immune reactivity to self nucleic acids" (WO/2008/076981, application # PCT/US2007/087787), related to this work.