Transcription-coupled and global genome repair differentially influence Ultraviolet-B induced acute skin effects and systemic immunosuppression
Exposure to UV-B radiation impairs immune responses in mammals by inhibiting especially Th1-mediated contact hypersensitivity and delayed-type hypersensitivity. Immunomodulation is not restricted to the exposed skin, but is also observed at distant sites, indicating the existence of mediating factors such as products from exposed skin cells or photoactivated factors present in the superficial layers. DNA damage appears to play a key role, because enhanced nucleotide excision repair (NER) strongly counteracts immunosuppression. To determine the effects of the type and genomic location of UV-induced DNA damage on immunosuppression and acute skin reactions (edema and erythema) four congenic mouse strains carrying different defects in NER were compared: CSB and XPC mice lacking transcription-coupled or global genome NER, respectively, as well as XPA and TTD/XPD mice carrying complete or partial defects in both NER subpathways, respectively. The major conclusions are that 1) transcription-coupled DNA repair is the dominant determinant in protection against acute skin effects; 2) systemic immunomodulation is only affected when both NER subpathways are compromised; and 3) sunburn is not related to UV-B-induced immunosuppression.
|Keywords||*Genome, *Immunosuppression, *Ultraviolet Rays, 88-88-0 (Picryl Chloride), Animals, Cockayne Syndrome/genetics/immunology, DNA Repair/*immunology/radiation effects, Dermatitis, Contact/genetics/immunology, Dose-Response Relationship, Immunologic, Dose-Response Relationship, Radiation, Edema/genetics/immunology, Erythema/genetics/immunology, Hair Diseases/genetics/immunology, Hypersensitivity, Delayed/genetics/immunology/microbiology, Listeria monocytogenes/immunology/radiation effects, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Picryl Chloride/immunology, Skin/*immunology/metabolism/*radiation effects, Support, Non-U.S. Gov't, Support, U.S. Gov't, P.H.S., Transcription, Genetic/*immunology/radiation effects, Xeroderma Pigmentosum/genetics/immunology|
Garssen, J., van Steeg, H., de Gruijl, F.R., de Boer, J., van der Horst, G.T.J., van Kranen, H., … Hoeijmakers, J.H.J.. (2000). Transcription-coupled and global genome repair differentially influence Ultraviolet-B induced acute skin effects and systemic immunosuppression. Journal of Immunology, 164, 6199–6205. Retrieved from http://hdl.handle.net/1765/3173