Transcription-coupled and global genome repair differentially influence UV-B-induced acute skin effects and systemic immunosuppression

Exposure to UV-B radiation impairs immune responses in mammals by inhibitin g especially Th1-mediated contact hypersensitivity and delayed-type hyperse nsitivity. Immunomodulation is not restricted to the exposed skin, but is a lso observed at distant sites, indicating the existence of mediating factor s such as products from exposed skin cells or photoactivated factors presen t in the superficial layers. DNA damage appears to play a key role, because enhanced nucleotide excision repair (NER) strongly counteracts immunosuppr ession, To determine the effects of the type and genomic location of UV-ind uced DNA damage on immunosuppression and acute skin reactions (edema and er ythema) four congenic mouse strains carrying different defects in NER were compared: CSB and XPC mice lacking transcription-coupled or global genome N ER, respectively, as well as XPA and TTD/XPD mice carrying complete or part ial defects in both NER subpathways, respectively. The major conclusions ar e that 1) transcription-coupled DNA repair is the dominant determinant in p rotection against acute skin effects; 2) systemic immunomodulation is only affected when both NER subpathways are compromised; and 3) sunburn is not r elated to UV-B-induced immunosuppression.