Association of transcription-coupled repair but not global genome repair with ultraviolet-B-induced Langerhans cell depletion and local immunosuppression.
Exposure to ultraviolet-B radiation impairs cellular immune responses. This immunosuppression seems to be associated with Langerhans cell migration. DNA damage appears to play a key role because enhanced nucleotide excision repair, a pathway essential for elimination of ultraviolet-B-induced DNA lesions, strongly counteracts immunosuppression. To determine the effect of DNA repair on ultraviolet-B-induced local immunosuppression and Langerhans cell disappearance, three mouse strains carrying different defects in nucleotide excision repair were compared. XPC mice, which were defective in global genome repair, were as sensitive to ultraviolet-B-induced local suppression of contact hypersensitivity to picryl chloride as their wild-type littermates. CSB mice, defective in transcription-coupled repair, were far more sensitive for immunosuppression as were XPA mice, defective in both transcription-coupled repair and global genome repair. Only a moderate depletion of Langerhans cells was observed in XPC mice and wild-type littermates. Ultraviolet-B-induced Langerhans cell depletion was enhanced in CSB and XPA mice. Hence, the major conclusion is that local immunosuppression is only affected when transcription-coupled DNA repair is impaired. Furthermore, a defect in transcription-coupled repair was linked to enhanced ultraviolet-B-induced Langerhans cell depletion. In combination with earlier experiments, it can be concluded that Langerhans cell disappearance is related to ultraviolet-B-induced local but not to systemic immunosuppression.
Kölgen
Wendy
W
Department of Dermatology, University Medical Center Utrecht, Utrecht, The Netherlands. wkolgen@yahoo.com
van Steeg
Harry
H
van der Horst
Gijsbertus T J
GT
Hoeijmakers
Jan H J
JH
van Vloten
Willem A
WA
de Gruijl
Frank R
FR
Garssen
Johan
J
D000818:Animals; D015415:Biomarkers; D002465:Cell Movement / Q000276:immunology; D004260:DNA Repair / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000235:genetics; D004307:Dose-Response Relationship, Radiation; D007107:Immune System / Q000276:immunology / Q000528:radiation effects*; D007801:Langerhans Cells / Q000166:cytology* / Q000276:immunology / Q000528:radiation effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D014158:Transcription, Genetic / Q000276:immunology; D014466:Ultraviolet Rays / Q000009:adverse effects; D051760:Xeroderma Pigmentosum Group A Protein
D015415:Biomarkers; D004268:DNA-Binding Proteins; D011948:Receptors, Antigen, T-Cell; D051760:Xeroderma Pigmentosum Group A Protein; C497315:Xpa protein, mouse; C501002:Xpc protein, mouse