Cyclobutane pyrimidine dimer formation is a molecular trigger for solar-simulated ultraviolet radiation-induced suppression of memory immunity in humans.
We tested the hypothesis that DNA is a target for solar-simulated ultraviolet radiation (ssUVR)-induced suppression of the reactivation of memory immunity in humans. T4N5 liposomes contain the DNA repair enzyme T4 endonuclease V. This cleaves DNA at the site of ultraviolet radiation (UVR)-induced cyclobutane pyrimidine dimers (CPD), initiating DNA repair. It has previously been used to show that CPDs are a key molecular trigger for UVR-induced immunosuppression in mice. To determine whether CPD formation is involved in UVR immunosuppression in humans, nickel-allergic volunteers were irradiated with a range of doses of ssUVR. T4N5 or empty liposomes were then applied after irradiation. Nickel-induced recall immunity was assessed by reflectance spectrometry. T4N5 liposomes inhibited immunosuppression and prevented ssUVR from reducing the number of epidermal dendritic cells. T4N5 liposomes also reduced macrophage infiltration into irradiated epidermis. These studies show that enhanced removal of CPDs from human skin protects from immunosuppression, hence demonstrating that these photolesions are an important molecular event in ssUVR-induced immunosuppression in humans. CPDs also triggered loss of dendritic cells and infiltration by macrophages. It is possible that these changes to antigen presenting cells contribute to ssUVR induced suppression of recall immunity to nickel in humans.
Kuchel
Johanna M
JM
Dermatology Laboratories, The Melanoma and Skin Cancer Research Institute, Sydney Cancer Centre, The University of Sydney at Royal Prince Alfred Hospital, Blackburn Building, D06, Sydney, NSW 2006, Australia.
Barnetson
Ross St C
RS
Halliday
Gary M
GM
D000328:Adult; D004249:DNA Damage; D004260:DNA Repair; D043224:Deoxyribonuclease (Pyrimidine Dimer) / Q000008:administration & dosage / Q000378:metabolism; D003877:Dermatitis, Contact / Q000276:immunology; D005260:Female; D006801:Humans; D007156:Immunologic Memory / Q000528:radiation effects*; D008081:Liposomes; D008297:Male; D009532:Nickel / Q000276:immunology; D011740:Pyrimidine Dimers / Q000502:physiology*; D013472:Sunlight; D014466:Ultraviolet Rays; D014764:Viral Proteins / Q000008:administration & dosage / Q000378:metabolism
D008081:Liposomes; D011740:Pyrimidine Dimers; D014764:Viral Proteins; D009532:Nickel; C470698:endonuclease V, phage T4; D043224:Deoxyribonuclease (Pyrimidine Dimer)