Increased Levels of Interleukin-17A Exosomes in Psoriasis

Abstract

Exosomes are naturally occurring small membrane-enclosed nanovesicles that modulate the immune system and mediate communication between cells and the transport of cellular components. Although the field of exosome research in cancer progression is expanding, there are very few studies on the role of exosomes in immune-mediated inflammatory diseases. This study shows, for the first time, the presence of circulating exosomes in patients with psoriasis, in particular in those with moderate-to-severe psoriasis, through IL-17A-producing exosomes. Further larger studies are required, to evaluate the effect of systemic treat ments on exosome production. Exosomes are involved in modulating the immune system and mediating communication between cells. The aim of this study was to investigate the involvement of exosomes in psoriasis. Exosomes from patients with psoriasis were analysed by nanoparticle tracking analysis and protein expression was analysed by western blotting. The concentration of HSP70 was determined by an enzyme-linked immunosorbent assay, and concentrations of interleukin (IL)-1β, IL-2, IL-6, IL-10, IL-17A and tumour necrosis factor alpha (TNF-α) were determined by flow cytometry. Based on the severity of psoriasis, evaluated by body surface area (≤ 10% vs. > 10%), 2 groups of patients were compared (49 with mild psoriasis and 71 with moderate-to-severe psoriasis). The number (2.52×10 11 ± 2.29×10 10 vs. 1.79×10 11 ± 1.93×10 10 , p = 0.19) and size (94.44 ± 22.00 nm vs. 96.87 ± 28.30 nm, p = 0.72) of exosomes and the concentration of HSP70 in the exosomes were not significantly different in the 2 groups of patients. IL-17A exosome levels were significantly higher in patients with moderate-to-severe psoriasis compared with those with mild psoriasis (p = 0.02). There were no significant differences in levels of TNF-α, IL-1, IL-2, IL-6 and IL-10. This study shows, for the first time, the presence of circulating exosomes in patients with psoriasis. These data confirm the involvement of circulating exosomes in psoriasis, in particular in moderate-to-severe psoriasis, through IL-17A-producing exosomes.

Application of imiquimod-induced murine psoriasis model in evaluating interleukin-17A antagonist

“…By illustrating plasma IL6 kinetics and its relationship with IL17A, we determined the availability of IL6 as PD marker to illustrate the IL17A signaling status [29][30][31], by which the successful antagonization of IL17A resulted in distinct IL6 suppression 0.5 h after IMQ application. The kinetical character of IL17A/IL6 activation in this model is summarized in Fig.…”

Regulatory Role of Immune Cell-Derived Extracellular Vesicles in Cancer: The Message Is in the Envelope

“…To the best of our knowledge, there have been no reports on the immunomodulatory effects of IL-17-expressing sEVs from γδ T cells in cancer. Of note though, IL-17-containing sEVs were found at much higher levels in patients with moderate to severe psoriasis compared to those with mild psoriasis ( 187 ), suggesting that IL-17-containing sEVs may correlate with disease progression. Unfortunately, the cell type of origin for these IL-17-containing sEVs is unknown.…”

Extracellular Vesicles as Potential Theranostic Platforms for Skin Diseases and Aging

“…Emerging evidence highlights the immunologic role of IL-17, a pro-inflammatory cytokine secreted from T helper 17 cells (T h 17 cells) [13]. Levels of IL-17α in EVs of dermal dendritic cells (DCs) were correlated with the severity of the disease symptoms [14]. Additionally, microRNAs (miRNAs) contained within psoriatic keratinocyte EVs induce the polarization of T cells to a more inflamed state.…”