Extracellular vesicles in Inflammatory Skin Disorders: from Pathophysiology to Treatment

Shao, Shuai; Fang, Hui; Li, Qingyang; Wang, Gang

doi:10.7150/thno.45488

Cited by 41 publications

(54 citation statements)

References 254 publications

(263 reference statements)

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“…Identification of neutrophil-derived exosomes as a new subcellular entity could result in elucidation of a molecular player providing a fundamental link between neutrophil-driven inflammation and multi-organ tissue damage observed in ENL with far-reaching implications for future research. Neutrophil-derived exosomes have already been demonstrated as a new means of intercellular communication promoting extracellular matrix destruction in an array of chronic inflammatory lung disease and have key immunomodulatory roles in a variety of inflammatory dermatological disorders, justifying their role as biomarkers indicating a variety of pathophysiological states ( 109 – 111 ).…”

Section: Neutrophil Biologymentioning

confidence: 99%

Neutrophil NETworking in ENL: Potential as a Putative Biomarker: Future Insights

Sahu

Sharma

et al. 2021

Front. Med.

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Erythema nodosum leprosum (ENL), also known as type 2 reaction (T2R) is an immune complex mediated (type III hypersensitivity) reactional state encountered in patients with borderline lepromatous and lepromatous leprosy (BL and LL) either before, during, or after the institution of anti-leprosy treatment (ALT). The consequences of ENL may be serious, leading to permanent nerve damage and deformities, constituting a major cause of leprosy-related morbidity. The incidence of ENL is increasing with the increasing number of multibacillary cases. Although the diagnosis of ENL is not difficult to make for physicians involved in the care of leprosy patients, its management continues to be a most challenging aspect of the leprosy eradication program: the chronic and recurrent painful skin lesions, neuritis, and organ involvement necessitates prolonged treatment with prednisolone, thalidomide, and anti-inflammatory and immunosuppressive drugs, which further adds to the existing morbidity. In addition, the use of immunosuppressants like methotrexate, azathioprine, cyclosporine, or biologics carries a risk of reactivation of persisters (Mycobacterium leprae), apart from their own end-organ toxicities. Most ENL therapeutic guidelines are primarily designed for acute episodes and there is scarcity of literature on management of patients with chronic and recurrent ENL. It is difficult to predict which patients will develop chronic or recurrent ENL and plan the treatment accordingly. We need simple point-of-care or ELISA-based tests from blood or skin biopsy samples, which can help us in identifying patients who are likely to require prolonged treatment and also inform us about the prognosis of reactions so that appropriate therapy may be started and continued for better ENL control in such patients. There is a significant unmet need for research for better understanding the immunopathogenesis of, and biomarkers for, ENL to improve clinical stratification and therapeutics. In this review we will discuss the potential of neutrophils (polymorphonuclear granulocytes) as putative diagnostic and prognostic biomarkers by virtue of their universal abundance in human blood, functional versatility, phenotypic heterogeneity, metabolic plasticity, differential hierarchical cytoplasmic granule mobilization, and their ability to form NETs (neutrophil extracellular traps). We will touch upon the various aspects of neutrophil biology relevant to ENL pathophysiology in a step-wise manner. We also hypothesize about an element of metabolic reprogramming of neutrophils by M. leprae that could be investigated and exploited for biomarker discovery. In the end, a potential role for neutrophil derived exosomes as a novel biomarker for ENL will also be explored.

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Section: Neutrophil Biologymentioning

confidence: 99%

Neutrophil NETworking in ENL: Potential as a Putative Biomarker: Future Insights

Sahu

Sharma

et al. 2021

Front. Med.

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“…Another recent study has shown the involvement of EVs in dermatitis. It was observed that EV-associated α-Hemolysin secreted by S. aureus induced keratinocyte death, skin barrier disruption and inflammation (release IL-1β, IL-6, IL-8, and MIP-1α)—the key phenotypes associated with atopic dermatitis (AD) [ 172 , 173 , 174 ]. Additionally, it was found that there was an increase in the pro-inflammatory mediators, including IL-6, thymic stromal lymphopoietin (TSLP), MIP-1α, and eotaxin, in mouse dermal fibroblasts cells exposed to S. aureus EVs [ 175 ].…”

Section: Evs In Htlv-1-related Diseasesmentioning

confidence: 99%

Extracellular Vesicles in HTLV-1 Communication: The Story of an Invisible Messenger

Sharif

Pinto

Mensah

et al. 2020

Viruses

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Human T-cell lymphotropic virus type 1 (HTLV-1) infects 5–10 million people worldwide and is the causative agent of adult T-cell leukemia/lymphoma (ATLL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) as well as other inflammatory diseases. A major concern is that the most majority of individuals with HTLV-1 are asymptomatic carriers and that there is limited global attention by health care officials, setting up potential conditions for increased viral spread. HTLV-1 transmission occurs primarily through sexual intercourse, blood transfusion, intravenous drug usage, and breast feeding. Currently, there is no cure for HTLV-1 infection and only limited treatment options exist, such as class I interferons (IFN) and Zidovudine (AZT), with poor prognosis. Recently, small membrane-bound structures, known as extracellular vesicles (EVs), have received increased attention due to their potential to carry viral cargo (RNA and proteins) in multiple pathogenic infections (i.e., human immunodeficiency virus type I (HIV-1), Zika virus, and HTLV-1). In the case of HTLV-1, EVs isolated from the peripheral blood and cerebral spinal fluid (CSF) of HAM/TSP patients contained the viral transactivator protein Tax. Additionally, EVs derived from HTLV-1-infected cells (HTLV-1 EVs) promote functional effects such as cell aggregation which enhance viral spread. In this review, we present current knowledge surrounding EVs and their potential role as immune-modulating agents in cancer and other infectious diseases such as HTLV-1 and HIV-1. We discuss various features of EVs that make them prime targets for possible vehicles of future diagnostics and therapies.

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“…Abnormal microangiogenesis is closely related to the development of psoriasis (33). Microcirculation disturbances and hemorheological changes are observed in the skin lesions of psoriatic patients (34). In this study, we found that PSORI-CM02 inhibited the proliferation and migration of IL-17Astimulated HUVECs and reduced new blood vessel growth in the skin of mice with IMQ-induced psoriasis.…”

Section: Discussionmentioning

confidence: 51%

Anti-Angiogenic Efficacy of PSORI-CM02 and the Associated Mechanism in Psoriasis In Vitro and In Vivo

Yang

Zhang

et al. 2021

Front. Immunol.

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Psoriasis is a chronic proliferative autoimmune dermatologic disease characterised by abnormal angiogenesis. Thus, regulating angiogenesis in the skin is an important treatment strategy for psoriasis. PSORI-CM02, an empirical Chinese medicine formula optimised from Yin Xie Ling, was created by the Chinese medicine specialist, Guo-Wei Xuan. Clinical studies have shown that PSORI-CM02 is safe and effective for the treatment of psoriasis. However, its anti-psoriatic mechanisms remain to be further explored. In this study, we investigated the effects of PSORI-CM02 on angiogenesis in the skin and the underlying mechanisms in IL-17A-stimulated human umbilical vein endothelial cells (HUVECs) and a murine model of imiquimod (IMQ)-induced psoriasis. In vitro, PSORI-CM02 significantly inhibited the proliferation and migration of IL-17A-stimulated HUVECs in a dose-dependent manner. Further, it markedly regulated the antioxidative/oxidative status and inflammation; suppressed the expression of VEGF, VEGFR1, VEGFR2, ANG1, and HIF-1α; and reduced the phosphorylation of MAPK signalling pathway components in IL-17A-stimulated HUVECs. In vivo studies showed that PSORI-CM02 markedly reduced angiogenesis in the skin of mice with IMQ-induced psoriasis, while significantly rebalancing antioxidant/oxidant levels; inhibiting the production of IL-6, TNF-α, IL-17A, and IL-17F; and repressing the synthesis of angiogenic mediators. In addition, PSORI-CM02 markedly reduced the activation of the MAPK signalling pathway in psoriatic skin tissue. Taken together, our results demonstrated that PSORI-CM02 inhibited psoriatic angiogenesis by reducing the oxidative status and inflammation, suppressing the expression of angiogenesis-related molecules, and inhibiting the activation of the MAPK signalling pathway in vitro and in vivo.

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Extracellular vesicles in Inflammatory Skin Disorders: from Pathophysiology to Treatment

Cited by 41 publications

References 254 publications

Neutrophil NETworking in ENL: Potential as a Putative Biomarker: Future Insights

Neutrophil NETworking in ENL: Potential as a Putative Biomarker: Future Insights

Extracellular Vesicles in HTLV-1 Communication: The Story of an Invisible Messenger

Anti-Angiogenic Efficacy of PSORI-CM02 and the Associated Mechanism in Psoriasis In Vitro and In Vivo

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