Acta Dermato-Venereologica 99-12CompleteContent

1143 INVESTIGATIVE REPORT Increased Levels of Interleukin-17A Exosomes in Psoriasis Claire JACQUIN-PORRETAZ 1 , Marine CORDONNIER 2 , Charlée NARDIN 1,3 , Laura BOULLEROT 4 , Gaetan CHANTELOUP 2 , Valentin VAUTROT 2,3 , Olivier ADOTEVI 4 , Carmen GARRIDO 2 , Jessica GOBBO 2,5# and François AUBIN 1,3# Department of Dermatology, University Hospital, Besançon, 2 University of Bourgogne-Franche Comté, Inserm U1231, Dijon, 3 EA3181 and UMR Inserm 1098, University of Bourgogne-Franche Comté, Besançon, and 5 Department of Medical Oncology, Early Phase Units, Georges- François Leclerc Centre, Dijon, France # These authors contributed equally. 1 4 Exosomes are involved in modulating the immune sys- tem 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 ana- lysis and protein expression was analysed by western blotting. The concentration of HSP70 was determined by an enzyme-linked immunosorbent assay, and con- centrations 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 sig- nificantly different in the 2 groups of patients. IL-17A exosome levels were significantly higher in patients with moderate-to-severe psoriasis compared with tho- se with mild psoriasis (p = 0.02). There were no signifi- cant differences in levels of TNF-α, IL-1, IL-2, IL-6 and IL-10. This study shows, for the first time, the presen- ce of circulating exosomes in patients with psoriasis. These data confirm the involvement of circulating exo- somes in psoriasis, in particular in moderate-to-severe psoriasis, through IL-17A-producing exosomes. Key words: exosomes; psoriasis; IL-17. Accepted Aug 22, 2019; E-published Aug 22, 2019 Acta Derm Venereol 2019; 99: 1143–1147. Corr: François Aubin, Department of Dermatology, University Hospital, 3 Bd Fleming, FR-25030 Besançon, France. E-mail: francois.aubin@univ- fcomte.fr E xosomes are naturally occurring small membrane- enclosed nanovesicles with a characteristic diameter of 30–120 nm, which are constitutively generated and released by various cells (1). Exosomes are shed from the surface of most cell types. They carry membrane components and contents from the cytoplasm of the cells from which they are released. Under normal cellular conditions, the release of exosomes accompanies normal cell growth and activation of some cellular functions, such as stimulation of T-cell growth in vitro and induc- tion of anti-tumour immune responses depending on SIGNIFICANCE Exosomes are naturally occurring small membrane-enclo- sed nanovesicles that modulate the immune system and mediate communication between cells and the transport of cellular components. Although the field of exosome re- search 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 pso- riasis, in particular in those with moderate-to-severe pso- riasis, through IL-17A-producing exosomes. Further larger studies are required, to evaluate the effect of systemic treatments on exosome production. the specific cell type (2). These vesicles contain various DNA (3), miRNA (4) and proteins (5). They can enter the bloodstream and act as messengers between cells (1). Although the field of exosome research in cancer progression is expanding, there are very few studies into the role of exosomes in immune-mediated inflammatory diseases (6, 7). Psoriasis is a chronic, autoimmune skin disease associated with a T-helper-17 response induced by the release of IL-23 from myeloid epidermal dendritic cells, leading to proliferation of keratinocytes, resulting in psoriatic plaque formation (8). Although recent biologic agents targeting different pro-inflammatory cytokines have revolutionized the management of psoriasis, these agents do not address the causes of the abnormal immunoregulatory responses of the disease, because the aetiology is not yet completely understood. The 70-kDa heat shock proteins (HSP70) are known to be potent immunomodulators, and their anti-inflammatory activity has recently been investigated in a murine psoriasis-like model (9). Since exosomes can modulate the immune system and mediate communication between cells and the transport of cellular components, such as cytokines and HPS70 (10), the aim of this study was to investigate their invol- vement in psoriasis. PATIENTS AND METHODS Patients The study design was approved by the local research ethics committee and written informed consent was provided before This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2019 Acta Dermato-Venereologica. doi: 10.2340/00015555-3300 Acta Derm Venereol 2019; 99: 1143–1147

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