Abstract
Neutrophil extracellular traps (NETs) have been implicated in the development of certain immune-mediated diseases, but their role in psoriasis has not been clearly defined. Human β-defensin-2 (HBD-2) is an important antimicrobial peptide overexpressed in psoriasis epidermis. We evaluated whether the amount of NETs is increased in psoriasis and determined the effect of NETs on HBD-2 production in epidermal keratinocytes. Using fluorescent microscopy, we found that patients with psoriasis (n = 48) had higher amount of NETotic cells in their peripheral blood compared to healthy controls (n = 48) and patients with eczema (n = 35). Psoriasis sera showed increased ability to induce NET formation in control neutrophils but normal NET degradation ability. The amount of NETs in the peripheral blood correlated with psoriasis disease severity. NETosis was also observed in the majority (18 of 20) of psoriasis skin specimens. Furthermore, NETs induced HBD-2 mRNA and protein production in keratinocytes, and immunohistochemical analysis confirmed strong expression of HBD-2 in psoriasis lesional skin. In summary, NET formation is increased in peripheral blood and lesional skin of psoriasis patients and correlates with disease severity. Additionally, NET-induced HBD-2 production may provide a novel mechanism for the decreased susceptibility of psoriasis plaques to microbial infections.
Highlights
Recently been found to inhibit neutrophil functions[16]
Since our findings revealed that neutrophil extracellular traps (NETs) were present within psoriatic epidermis in close proximity to keratinocytes which expressed HBD-2, we investigated whether netting neutrophils from psoriasis patients may induce HBD-2 expression in epidermal keratinocytes
Psoriasis may appear at any age, but it is uncommonly seen under the age of 10 years, and is most likely to start between 15–30 years
Summary
Recent studies showed that neutrophils express IL-17 in psoriasis skin lesions, suggesting that these cells may play a role in psoriasis pathogenesis[17,18]. NETs are web-like structures which consist of decondensed DNA associated with histones and antimicrobial peptides[20,21,22,23]. They are derived from the granular and nuclear contents of neutrophils. It is well known that psoriasis patients have a low incidence of cutaneous infections[31] This may be explained by the increased expression of various antimicrobial peptides in psoriasis skin lesions[32]. The findings of this study provided new insights into the significance of NETosis in the pathophysiology of psoriasis, the role of NETosis in the antimicrobial defense mechanisms of this disease
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