The Immune-Modulating Cytokine and Endogenous Alarmin Interleukin-33 Is Upregulated in Skin Exposed to Inflammatory UVB Radiation

Abstract

The cellular and molecular mechanisms by which UV radiation modulates inflammation and immunity while simultaneously maintaining skin homeostasis is complex and not completely understood. Similar to the effects of UV, IL-33 has potent immune-modulating properties that are mediated by the downstream induction of cytokines and chemokines. We have discovered that exposure of mice in vivo or human skin samples ex vivo to inflammatory doses of UVB induced IL-33 expression within the epidermal and dermal skin layers. Using a combination of murine cell lines and primary human cells, we demonstrate that both UV and the oxidized lipid platelet activating factor induce IL-33 expression in keratinocytes and dermal fibroblasts. Highlighting the significance of these results, we found that administering IL-33 to mice in vivo suppressed the induction of Th1-mediated contact hypersensitivity responses. This may have consequences for skin cancer growth because UV-induced squamous cell carcinomas that evade immunological destruction were found to express significantly higher levels of IL-33. Finally, we demonstrate that dermal mast cells and skininfiltrating neutrophils closely associate with UV-induced IL-33-expressing fibroblasts. Our results therefore identify and support a role for IL-33 as an important early danger signal produced in response to inflammation-inducing UV radiation.

The IL-33/ST2 axis: Role in health and disease

“…IL-33 is expressed in healthy skin, predominantly as the fulllength precursor [89,90], and skin cells exposed to inflammatory cytokines, infectious agents such as Staphylococcus aureus, or UVB radiation, produce high levels of IL-33 mRNA [89,91]. In a S. aureus infection model in mouse skin, high levels of IL-33 were produced by macrophages that subsequently induced an antimicrobial state through nitric oxide generation [89].…”

TCRVγ9 γδ T Cell Response to IL-33: A CD4 T Cell–Dependent Mechanism

“…IL-33 is constitutively expressed by HEVs (12), but also by endothelial cells in many normal human tissues, by dermal fibroblasts and keratinocytes, and by epithelial cells in tissues exposed to the environment (15,16). IL-33 is also overexpressed in some circumstances such as during mechanical or UV stress (17,18) and in inflammatory and autoimmune diseases such as asthma (19,20). Furthermore, IL-33 is abundantly expressed in the nucleus of endothelial cells in human tumors of the kidney, stomach, liver, and pancreas (15).…”

Fotoimmünoloji

“…Keratinosit kökenli IL-10, UV ışımasına bağlı immünsupresyonda önemli rol oynar 2,33,34 . Keratinosit kökenli IL-33 de immünsupresyona neden olabilir 35 . UV ışıması ile keratinositler PAF sekresyonu yapabilirler ve PAF, UV ile uyarılan immünsupresyonla ilişkili bulunmuştur 36,37 .…”

“…UV ışımasıyla keratinositlerden PAF salgılanır ve PAF, UV ile uyarılan immünsupresyonla ilişkilidir 2 . PAF, IL-33 sekresyonunu uyarmak yoluyla da immünsupresyona neden olabilir 40 40 . Kompleman Deride kompleman komponentlerinin aktivasyonu UV ile uyarılan immünsupresyona katkıda bulunur 43,44 .…”