Murine lupus is neutrophil elastase-independent in the MRL.Faslpr model.

Autor: Gordon RA; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America., Tilstra JS; Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America., Marinov A; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America., Nickerson KM; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America., Bastacky SI; Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America., Shlomchik MJ; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2020 Apr 03; Vol. 15 (4), pp. e0226396. Date of Electronic Publication: 2020 Apr 03 (Print Publication: 2020).
DOI: 10.1371/journal.pone.0226396
Abstrakt: Loss of tolerance to nuclear antigens and multisystem tissue destruction is a hallmark of systemic lupus erythematosus (SLE). Although the source of autoantigen in lupus remains elusive, a compelling hypothetical source is dead cell debris that drives autoimmune activation. Prior reports suggest that neutrophil extracellular traps (NETs) and their associated death pathway, NETosis, are sources of autoantigen in SLE. However, others and we have shown that inhibition of NETs by targeting the NADPH oxidase complex and peptidylarginine deiminase 4 (PADI4) did not ameliorate disease in spontaneous murine models of SLE. Furthermore, myeloperoxidase and PADI4 deletion did not inhibit induced lupus. Since NET formation may occur independently of any one mediator, to address this controversy, we genetically deleted an additional important mediator of NETs and neutrophil effector function, neutrophil elastase (ELANE), in the MRL.Faslpr model of SLE. ELANE deficiency, and by extension ELANE-dependent NETs, had no effect on SLE nephritis, dermatitis, anti-self response, or immune composition in MRL.Faslpr mice. Taken together with prior data from our group and others, these data further challenge the paradigm that NETs and neutrophils are pathogenic in SLE.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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