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NET Formation Implicated in Myositis

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NET Formation Implicated in Myositis RESEARCH HIGHLIGHTS MYOSITIS looked at the effects of NETs on muscle myotubes (formed from treatment of precursor myoblasts in vitro). NET formation normal-density NETs isolated from patients with IIM impaired the viability granulocytes of the skeletal myotubes in vitro, implicated in myositis with anti- but did not reduce myoblast A distinct subset of neutrophils antibodies against melanoma MDA5 anti- proliferation. called low-density granulocytes differentiation-associated protein 5 bodies The damaging in vitro … effects of NETs were mediated (LDGs) contribute to the patho- (MDA5). Notably, treatment promoted NET genesis of a number of systemic of normal-density granulocytes in part by citrullinated histones autoimmune diseases, including with anti-MDA5 antibodies isolated formation (a compo nent of NETs) and could systemic lupus erythematosus, from patients with IIM promoted be partially inhibited with an in part through the formation NET formation in vitro. anti-histone H4 antibody. Impor- of neutrophil extracellular traps RNA sequenc- tantly, treatment with citrullinated (NETs). New findings implicate ing analysis iden- H4, but not treatment with aberrant NET formation by tified a neutrophil native H4, was toxic to myotubes, LDGs in idiopathic inflammatory gene signature in recapitulating the effects of NETs myopathies (IIM). the skeletal muscle in vitro. “We found that the presence of patients with “Our results implicate neutro phil of LDGs and NETs associates with derma tomyositis dysregulation in the pathogenesis clinical features of IIM and that (a subtype of IIM) of adult and childhood-onset NETs are elevated in the circulation that was associated IIM and suggest that targeting and various organs of patients with the expression of pathways of NET formation could with IIM,” reports Mariana Kaplan, type I and type II have therapeutic roles in this corresponding author on the new interferon-regulated disease,” concludes Kaplan. study. Increased levels of circulating genes as well as indica- Jessica McHugh NETs were associated with disease tors of muscle damage. ORIGINAL ARTICLE Seto, N. L. et al. Neutrophil activity as well as with the presence To investigate the dysregulation is pathogenic in idiopathic of certain myositis-associated pathogenic role of NETs inflammatory myopathies. JCI Insight https:// doi.org/10.1172/jci.insight.134189 (2020) antibodies — in particular, in IIM, the researchers Limited Nature Smith/Springer N. Credit: SYSTEMIC LUPUS ERYTHEMATOSUS LDL subfraction linked to vascular ageing and heart disease in SLE Patients with systemic lupus erythe- atherosclerosis in response to LDL from matosus (SLE) have signs of early vas- patients with SLE, but not in response cular ageing and an increased risk of to LDL from healthy individuals. cardio vascular disease, but do not have “We found a high content of lysophos- increased concentrations of low-density phatidylcholine and platelet-activating lipoprotein (LDL) in their blood com- factor in the total LDL preparations pared with healthy individuals. LDL from patients with SLE, especially in Library Photo KULYK/Science MEHAU Credit: can be separated into five increasingly the L5 subfractions,” say corresponding to the damaged endothelium, electronegative subfractions (L1–L5), authors Liang-Yin Ke, Jeng-Hsien which facilitates their penetration of which L5 is known to be atherogenic. patients Yen and Chu-Huang Chen. “These into the subendothelium,” explains For the first time, researchers have exam- with SLE had inflammatory mediators can lead to first author Hua-Chen Chan. “This ined the L5 subfraction from patients less total the differentiation of monocytes into cascade of events, induced by L5 LDL, with SLE and investigated its role in pro-inflammatory CD16+ cells.” contributes to endothelial dysfunction SLE-associated cardiovascular changes. plasma LDL CD16+ monocytes were present and vascular ageing, thereby providing In the new study, patients with SLE than healthy at increased numbers in the blood a novel explanation for the early had less total plasma LDL than healthy individuals of patients with SLE compared with onset of atherosclerosis-associated individuals but a higher percentage of healthy individuals. Interestingly, both complications in patients with SLE,” the L5 subfraction, which correlated but a higher plasma concentrations of the chemo- she concludes. with clinical measures of vascular age- percentage kine CX3CL1 and expression of its Joanna Clarke ing. The researchers tested the athero- receptor CX CR1 on CD16+ monocytes of the L5 3 ORIGINAL ARTICLE Chan, H.-C. et al. Role of genic properties of LDL from patients were also increased in patients with low-density lipoprotein in early vascular aging with SLE by injecting it into Apoe–/– subfraction SLE compared with healthy individuals. associated with systemic lupus erythematosus. Arthritis Rheumatol. https://doi.org/10.1002/ mice. These atherosclerosis-prone mice “Through CX3CL1–CX3CR1 inter- art.41213 (2020) developed signs of vascular ageing and actions, CD16+ monocytes adhere NATURE REVIEWS | RHEUMATOLOGY VOLUME 16 | APRIL 2020 | 187.
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