Editors' ChoiceAutoimmunity

Send in the decoys: Cell-like particles ameliorate inflammatory autoimmune arthritis

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Science Translational Medicine  19 Sep 2018:
Vol. 10, Issue 459, eaav0341
DOI: 10.1126/scitranslmed.aav0341

Abstract

Neutrophil membrane–coated nanoparticles reduce symptoms of rheumatoid arthritis in mice.

Rheumatoid arthritis is a chronic, inflammatory, autoimmune disease that affects the joints. Early management of the chronic inflammation in the synovial membranes can prevent cartilage and joint destruction, however, current treatment approaches can lead to unsatisfactory clinical results. Although it is an autoantibody-driven disease, prior studies have shown a direct correlation between disease remissions and a reduced neutrophil response. Zhang et al. report a neutrophil cell membrane–coated nanoparticle system that induced a broad spectrum anti-inflammatory response and ameliorates inflammatory arthritis.

Joint inflammation and influx of immune cells is a hallmark of rheumatoid arthritis. Of all the immune cells implicated in the pathology of the disease, neutrophils play a multifactorial role, including progression of the disease by releasing degradative enzymes and reactive oxygen species. The neutrophils recruited into the joint space contribute to the cytokine and chemokine cascades that accompany inflammation and regulate immune responses via membrane-based interactions. The investigators reasoned that instead of tackling one inflammatory component at a time, a more effective translational approach could be the use of a nanoparticle that can neutralize a broad spectrum of inflammatory cytokines in the joint space. The research team isolated membranes from circulating neutrophils and developed PLGA nanoparticles with fused membranes to use as neutrophil decoys. The neutrophil-like nanoparticles bound with immunoregulatory molecules in vitro and conferred chondroprotection in vivo; enhanced cartilage penetration was observed compared with red blood cell–fused nanoparticles. When injected into the joints, the nanoparticles ameliorated joint destruction in a mouse model of collagen-induced arthritis and a tumor necrosis factor–α transgenic mouse model of inflammatory arthritis, similar to other treatments such as systemic cytokine blockade. Importantly, the authors established the anti-arthritis effectiveness of neutrophil membrane–fused nanoparticles in mice with early-stage arthritis following a prophylactic regimen to establish a preventive, broad applicability. The authors also developed human neutrophil nanoparticles and established the in vitro efficacy by neutralizing the inflammatory cascade in human synovial fluid specimens, followed by reduced activation of chondrocytes and endothelial cells. Although effective, it remains unclear whether the particulate system immunomodulates other immune cells in the synovial joint and whether the patient neutrophil membranes could contain citrullinated autoantigens found in neutrophil extracellular traps that drive the autoimmune processes underlying this disease.

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