568 Neutrophil NETosis is involved in UVB induced-skin inflammation

Abstract

Excessive exposure to UVB in sunlight causes photodamage that triggers autoimmune skin inflammation. Skin inflammation can exacerbate photodamage and, if recurring or long-lasting, can induce pathogenic alterations. The responses to UVB exposure include the release of inflammatory cytokines, including TNF-α, from keratinocytes, and the recruitment of inflammatory cells to the skin. Neutrophils are the first group of immune cells to be recruited to the site of photodamage, prior to the infiltration of monocyte/macrophages and lymphocytes. Accumulating evidence indicates the important roles of neutrophils in sterile inflammation, however, little is known about their involvement in UVB-induced skin inflammation. Neutrophil NETosis is a newly characterized neutrophil cell death that releases neutrophil extracellular traps (NETs). NETs have been detected in the lupus skin. NETs exhibit IL-17, and drive type I interferon (IFN) release from pDCs. These two important cytokines interact together to sustain and amplify autoimmune and inflammatory responses in lupus pathogenesis. However, the role of neutrophil NETosis in UVB-induced skin inflammation has not been explored. In the current study, we found that exposure of female C57/BL6 wild-type (WT) mice to UVB (250 mJ/cm2/day) for 5 consecutive days can induce skin inflammation with increased NETotic neutrophils. Our preliminary studies showed that these NETotic structures in the UVB-irradiated skin also exhibit proinflammatory cytokine IL-17. In searching for a relevant stimulus that mediates neutrophil NETosis in UVB-exposed WT mice, we found that TNFα was upregulated in UVB-irradiated skin. In addition, treatment of human primary neutrophils with TNFα in vitro can induce neutrophil NETosis. Therefore, our studies indicate that UVB exposure of mice can induce skin inflammation with increased NETotic neutrophils, which exhibit proinflammatory cytokine IL-17. UVB-induced TNF-α may mediate neutrophil NETosis in the inflamed skin.