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Abstract Number: 0287

RNA Externalized by Neutrophil Extracellular Traps Promotes Inflammatory Pathways in Endothelial Cells

Xinghao Wang1, Philip Carlucci2, Jorge Romo-Tena1, Jose Torres-Ruiz1, Hong-Wei Sun1, Markus Hafner1, Mariana Kaplan3 and Luz Blanco4, 1NIAMS, National Institute of Health, Bethesda, 2New York University School of Medicine, New York, NY, 3National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD, 4National Institute of Arthritis and Musculoskeletal and Skin Diseases, Centreville

Meeting: ACR Convergence 2020

Keywords: autoimmune diseases, innate immunity, interferon, neutrophils, Systemic lupus erythematosus (SLE)

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Session Information

Date: Friday, November 6, 2020

Session Title: SLE – Etiology & Pathogenesis Poster

Session Type: Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: Neutrophil extracellular traps (NETs) are extracellular lattices composed of nucleic material bound to neutrophil granule proteins. NETs may play pathogenic roles in development and severity of autoimmune diseases such as systemic lupus erythematosus (SLE), at least in part, through induction of type I interferon (IFN) responses via externalization of oxidized immunostimulatory DNA. A distinct subset of SLE proinflammatory neutrophils (low density granulocytes; LDGs) displays enhanced ability to form proinflammatory NETs that damage the vasculature.  We assessed whether NET-bound RNA can contribute to inflammatory responses in endothelial cells and the pathways that mediate this effect.

Methods: Expression of newly-synthesized RNA was quantified if healthy control and lupus NETs. The ability of endothelial cells to take up NET-bound RNA and downstream induction of type I IFN responses was quantified. RNAs present in NETs were sequenced and specific small RNAs were tested for induction of endothelial type I IFN pathways.

Results: NETs extruded newly-synthesized RNA that was internalized by endothelial cells and this was enhanced when NET nucleic acids were oxidized, particularly in lupus LDG NETs. Internalization of NET-bound RNA by endothelial cells was dependent on endosomal TLRs and the actin cytoskeleton and induced type I IFN stimulated genes (ISGs). This ISG induction was dependent on NET-associated miR-let7b, a small RNA expressed at higher levels in LDG NETs, which acted as a TLR7 agonist.

Conclusion: These results highlight underappreciated roles for small RNAs externalized in NETs in the induction of proinflammatory responses in vascular cells, with implications to lupus vasculopathy.


Disclosure: X. Wang, None; P. Carlucci, None; J. Romo-Tena, None; J. Torres-Ruiz, None; H. Sun, None; M. Hafner, None; M. Kaplan, None; L. Blanco, None.

To cite this abstract in AMA style:

Wang X, Carlucci P, Romo-Tena J, Torres-Ruiz J, Sun H, Hafner M, Kaplan M, Blanco L. RNA Externalized by Neutrophil Extracellular Traps Promotes Inflammatory Pathways in Endothelial Cells [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/rna-externalized-by-neutrophil-extracellular-traps-promotes-inflammatory-pathways-in-endothelial-cells/. Accessed March 2, 2021.
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