Proinflammatory Differentiation of Macrophages Through Microparticles That Form Immune Complexes Leads to T- and B-Cell Activation in Systemic Autoimmune Diseases

Burbano, Catalina; Villar-Vesga, Juan; Vásquez, Gloría; Muñoz-Vahos, Carlos Horacio; Rojas, Mauricio; Castaño, Diana

doi:10.3389/fimmu.2019.02058

Cited by 34 publications

(22 citation statements)

References 79 publications

(121 reference statements)

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“…Extracellular vesicles were isolated from citrate-induced anticoagulated peripheral blood and cerebrospinal fluid (CSF), as previously was described in our recent investigations ( Burbano et al, 2018a,b , 2019 ; Villar-Vesga et al, 2019 ). Briefly, blood samples were centrifuged immediately after collection at 1,800 × g for 10 min at 21°C to separate the plasma.…”

Section: Methodsmentioning

confidence: 99%

Differential Profile of Systemic Extracellular Vesicles From Sporadic and Familial Alzheimer’s Disease Leads to Neuroglial and Endothelial Cell Degeneration

Villar-Vesga

Henao‐Restrepo

Voshart

et al. 2020

Front. Aging Neurosci.

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Evidence suggests that extracellular vesicles (EVs) act as mediators and biomarkers of neurodegenerative diseases. Two distinct forms of Alzheimer disease (AD) are known: a late-onset sporadic form (SAD) and an early-onset familial form (FAD). Recently, neurovascular dysfunction and altered systemic immunological components have been linked to AD neurodegeneration. Therefore, we characterized systemic-EVs from postmortem SAD and FAD patients and evaluated their effects on neuroglial and endothelial cells. We found increase CLN-5 spots with vesicular morphology in the abluminal portion of vessels from SAD patients. Both forms of AD were associated with larger and more numerous systemic EVs. Specifically, SAD patients showed an increase in endothelial- and leukocyte-derived EVs containing mitochondria; in contrast, FAD patients showed an increase in platelet-derived EVs. We detected a differential protein composition for SAD- and FAD-EVs associated with the coagulation cascade, inflammation, and lipid-carbohydrate metabolism. Using mono- and cocultures (endothelium-astrocytes-neurons) and human cortical organoids, we showed that AD-EVs induced cytotoxicity. Both forms of AD featured decreased neuronal branches area and astrocytic hyperreactivity, but SAD-EVs led to greater endothelial detrimental effects than FAD-EVs. In addition, FAD- and SAD-EVs affected calcium dynamics in a cortical organoid model. Our findings indicate that the phenotype of systemic AD-EVs is differentially defined by the etiopathology of the disease (SAD or FAD), which results in a differential alteration of the NVU cells implied in neurodegeneration.

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Section: Methodsmentioning

confidence: 99%

Differential Profile of Systemic Extracellular Vesicles From Sporadic and Familial Alzheimer’s Disease Leads to Neuroglial and Endothelial Cell Degeneration

Villar-Vesga

Henao‐Restrepo

Voshart

et al. 2020

Front. Aging Neurosci.

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“…Of note, hemolytic environment and specifically the hemoglobin-activated platelets differentiate monocytes into pro-inflammatory M1-like macrophages (CD80 high ) (Singhal et al, 2018). Immune complexes from patients with systemic autoimmune diseases favor the polarization of monocyte-derived macrophages into a proinflammatory M1-like macrophages (Burbano et al, 2019). Some endogenous chemical compounds may play roles in monocytes differentiation.…”

Section: Macrophage Phenotypic Diversitymentioning

confidence: 99%

Macrophage Plasticity and Atherosclerosis Therapy

Lin

et al. 2021

Front. Mol. Biosci.

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Atherosclerosis is a chronic disease starting with the entry of monocytes into the subendothelium and the subsequent differentiation into macrophages. Macrophages are the major immune cells in atherosclerotic plaques and are involved in the dynamic progression of atherosclerotic plaques. The biological properties of atherosclerotic plaque macrophages determine lesion size, composition, and stability. The heterogenicity and plasticity of atherosclerotic macrophages have been a hotspot in recent years. Studies demonstrated that lipids, cytokines, chemokines, and other molecules in the atherosclerotic plaque microenvironment regulate macrophage phenotype, contributing to the switch of macrophages toward a pro- or anti-atherosclerosis state. Of note, M1/M2 classification is oversimplified and only represent two extreme states of macrophages. Moreover, M2 macrophages in atherosclerosis are not always protective. Understanding the phenotypic diversity and functions of macrophages can disclose their roles in atherosclerotic plaques. Given that lipid-lowering therapy cannot completely retard the progression of atherosclerosis, macrophages with high heterogeneity and plasticity raise the hope for atherosclerosis regression. This review will focus on the macrophage phenotypic diversity, its role in the progression of the dynamic atherosclerotic plaque, and finally discuss the possibility of treating atherosclerosis by targeting macrophage microenvironment.

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“…In addition to the abnormal activity of T and B cells, the imbalance of macrophage subsets is emerging to be an important player in the development of SLE ( 20 ). Therefore, inducing monocytes to preferentially shift from an inflammatory M1-like phenotype into an immunosuppressive M2-like phenotype may be a potential therapeutic strategy.…”

Section: Resultsmentioning

confidence: 99%

Increased Expression of PPAR-γ Modulates Monocytes Into a M2-Like Phenotype in SLE Patients: An Implicative Protective Mechanism and Potential Therapeutic Strategy of Systemic Lupus Erythematosus

et al. 2021

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Systemic lupus erythematosus (SLE) is a spectrum of autoimmune disorders characterized by continuous inflammation and the production of autoantibodies. Monocytes, as precursors of dendritic cells and macrophages, are involved in the pathogenesis of SLE, particularly in the inflammatory reactions. Previous studies have proved that Pam3CSK4, as a synthetic ligand of TLR2, could stimulate monocytes to differentiated into a M2-like phenotype which presented immunosuppressive functions. However, the underlying mechanisms remain to be further studied. Here, we reported an increased expression of PPAR-γ in the CD14+ monocytes from SLE patients, particularly in the treated group of SLE patients and the group with positive anti-dsDNA antibodies. Additionally, PPAR-γ expression decreased in the SLE patients with skin lesion. Furthermore, we demonstrated that Pam3CSK4 stimulation can decrease the expression of CCR7, CD80, IL-1β, IL-6, IL-12, and NF-κB which were related to the M1-like subset of monocytes and increased the expression of ARG1 which was related to the M2-like subset through upregulated PPAR-γ expression and consequently downregulated NF-κB expression in the CD14+ monocytes in a time-dependent manner. ChIP-qPCR results further demonstrated that Pam3CSK4 pretreatment could modulate PPAR-γ expression by regulating histone modification through the inhibition of Sirt1 binding to the PPAR-γ promoter. Taken together, our study indicated a protective role of TLR2/Sirt1/PPAR-γ pathway in the pathogenesis of SLE which provided potential therapeutic strategies.

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Proinflammatory Differentiation of Macrophages Through Microparticles That Form Immune Complexes Leads to T- and B-Cell Activation in Systemic Autoimmune Diseases

Cited by 34 publications

References 79 publications

Differential Profile of Systemic Extracellular Vesicles From Sporadic and Familial Alzheimer’s Disease Leads to Neuroglial and Endothelial Cell Degeneration

Differential Profile of Systemic Extracellular Vesicles From Sporadic and Familial Alzheimer’s Disease Leads to Neuroglial and Endothelial Cell Degeneration

Macrophage Plasticity and Atherosclerosis Therapy

Increased Expression of PPAR-γ Modulates Monocytes Into a M2-Like Phenotype in SLE Patients: An Implicative Protective Mechanism and Potential Therapeutic Strategy of Systemic Lupus Erythematosus

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