The Role and Impact of Extracellular Vesicles in the Modulation and Delivery of Cytokines during Autoimmunity

Hussain, Mumtaz; Iqbal, Asif; Norling, Lucy V.

doi:10.3390/ijms21197096

Cited by 18 publications

(6 citation statements)

References 153 publications

(162 reference statements)

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“…Autoimmune diseases are characterized by the production of specific autoantibodies resulting from the loss of immune tolerance, the recognition of self-antigens and the activation of T cells and B cells, and these lead to damage to multiple organs owing to a dysregulated adaptive immune response. Cytokines, such as TNFα, IL-1β, and IL-6, are involved in processes modulated by their delivery in extracellular vesicles 9,19,20 www.nature.com/scientificreports/ inflammasomes. Activation of the inflammasome leads to the cleavage of pro-interleukin (IL)-1β and the secretion of active IL-1β 21 .…”

Section: Esmentioning

confidence: 99%

Elevated G-CSF, IL8, and HGF in patients with definite Meniere’s disease may indicate the role of NET formation in triggering autoimmunity and autoinflammation

Zou

Zhao

Song

et al. 2022

Sci Rep

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The etiology and mechanism causing Meniere’s disease (MD) are not understood. The present study investigated the possible molecular mechanism of autoimmunity and autoinflammation associated with MD. Thirty-eight patients with definite MD and 39 normal volunteers were recruited, and 48 human cytokines/chemokines were quantified. In patients with MD pure tone audiograms, tympanograms and standard blood tests were performed. The mean hearing loss in the worse ear was 44.1 dB nHL. Compared to the referents, the concentrations of TNFα, IL1α, IL8, CTACK, MIP1α, MIP1β, G-CSF, and HGF in the sera of patients with MD were significantly elevated, while those of TRAIL and PDGFBB were significantly decreased. The area under the receiver operating characteristic curve (AUC) showed that G-CSF, MIP1α, and IL8 were above 0.8 and could be used to diagnose MD (p < 0.01), and the AUCs of CTACK and HGF were above 0.7 and acceptable to discriminate the MD group from the control group (p < 0.01). The revised AUCs (1 − AUC) of TRAIL and PDGFBB were above 0.7 and could also be used in the diagnosis of MD (p < 0.01). The linear regression showed significant correlations between MIP1α and GCSF, between IL2Rα and GCSF, between IL8 and HGF, between MIP1α and IL8, and between SCF and CTACK; there was a marginal linear association between IP10 and MIP1α. Linear regression also showed that there were significant age-related correlations of CTACK and MIG expression in the MD group (p < 0.01, ANOVA) but not in the control group. We hypothesize that G-CSF, IL8, and HGF, which are involved in the development of neutrophil extracellular traps (NETs) and through various mechanisms influence the functions of macrophages, lymphocytes, and dendritic cells, among others, are key players in the development of EH and MD and could be useful in elucidating the pathophysiological mechanisms leading to MD. Biomarkers identified in the present study may suggest that both autoimmune and autoinflammatory mechanisms are involved in MD. In the future, it will be valuable to develop a cost-effective method to detect G-CSF, IL8, HGF, CTACK, MIP1α, TRAIL, and PDGFBB in the serum of patient that have diagnostic relevance.

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Section: Esmentioning

confidence: 99%

Elevated G-CSF, IL8, and HGF in patients with definite Meniere’s disease may indicate the role of NET formation in triggering autoimmunity and autoinflammation

Zou

Zhao

Song

et al. 2022

Sci Rep

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“…All these nanometer-sized vesicles are actively secreted into biofluids, such as plasma, serum, CSF, saliva or urine, by multiple types of cells, and carry specific cargo, which is enriched with small noncoding RNAs, such as miRNAs. Although their exact role is mostly unknown, extracellular vesicles have been implicated in inflammatory diseases [ 135 , 136 ], cancer [ 137 , 138 ], and neurodegeneration [ 139 , 140 ], and their involvement in mental disorders is now under investigation [ 131 ]. For instance, high-throughput miRNA sequencing analysis identified a set of 12 upregulated and 20 downregulated miRNAs in serum exosomes of depressed patients [ 141 ].…”

Section: Mirna Studies Of Depression and Antidepressant Treatments Investigating Blood And Bodymentioning

confidence: 99%

The miRNome of Depression

Żurawek

Turecki

2021

IJMS

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Depression is an effect of complex interactions between genetic, epigenetic and environmental factors. It is well established that stress responses are associated with multiple modest and often dynamic molecular changes in the homeostatic balance, rather than with a single genetic factor that has a strong phenotypic penetration. As depression is a multifaceted phenotype, it is important to study biochemical pathways that can regulate the overall allostasis of the brain. One such biological system that has the potential to fine-tune a multitude of diverse molecular processes is RNA interference (RNAi). RNAi is an epigenetic process showing a very low level of evolutionary diversity, and relies on the posttranscriptional regulation of gene expression using, in the case of mammals, primarily short (17–23 nucleotides) noncoding RNA transcripts called microRNAs (miRNA). In this review, our objective was to examine, summarize and discuss recent advances in the field of biomedical and clinical research on the role of miRNA-mediated regulation of gene expression in the development of depression. We focused on studies investigating post-mortem brain tissue of individuals with depression, as well as research aiming to elucidate the biomarker potential of miRNAs in depression and antidepressant response.

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“…EVs may contain various type of biological materials, such as nucleic acids (mRNA, miRNA, DNA), lipids, and proteins. Depending on their respective origin EVs may induce different responses within target cells, such as cell migration, apoptosis, and cytokine release [ 3 , 4 ]. Among others, EVs are known contributors to inflammatory responses as well as to inflammation-resolving effects [ 3 , 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Targeted Lipidomics for Characterization of PUFAs and Eicosanoids in Extracellular Vesicles

et al. 2022

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Lipids are increasingly recognized as bioactive mediators of extracellular vesicle (EV) functions. However, while EV proteins and nucleic acids are well described, EV lipids are insufficiently understood due to lack of adequate quantitative methods. We adapted an established targeted and quantitative mass spectrometry (LC-MS/MS) method originally developed for analysis of 94 eicosanoids and seven polyunsaturated fatty acids (PUFA) in human plasma. Additionally, the influence of freeze–thaw (FT) cycles, injection volume, and extraction solvent were investigated. The modified protocol was applied to lipidomic analysis of differently polarized macrophage-derived EVs. We successfully quantified three PUFAs and eight eicosanoids within EVs. Lipid extraction showed reproducible PUFA and eicosanoid patterns. We found a particularly high impact of FT cycles on EV lipid profiles, with significant reductions of up to 70%. Thus, repeated FT will markedly influence analytical results and may alter EV functions, emphasizing the importance of a standardized sample pretreatment protocol for the analysis of bioactive lipids in EVs. EV lipid profiles differed largely depending on the polarization of the originating macrophages. Particularly, we observed major changes in the arachidonic acid pathway. We emphasize the importance of a standardized sample pretreatment protocol for the analysis of bioactive lipids in EVs.

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The Role and Impact of Extracellular Vesicles in the Modulation and Delivery of Cytokines during Autoimmunity

Cited by 18 publications

References 153 publications

Elevated G-CSF, IL8, and HGF in patients with definite Meniere’s disease may indicate the role of NET formation in triggering autoimmunity and autoinflammation

Elevated G-CSF, IL8, and HGF in patients with definite Meniere’s disease may indicate the role of NET formation in triggering autoimmunity and autoinflammation

The miRNome of Depression

Targeted Lipidomics for Characterization of PUFAs and Eicosanoids in Extracellular Vesicles

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