TY - JOUR
T1 - Association of Transcription-Coupled Repair but Not Global Genome Repair with Ultraviolet-B-Induced Langerhans Cell Depletion and Local Immunosuppression
AU - Kölgen, Wendy
AU - Van Steeg, Harry
AU - Van Der Horst, Gijsbertus T.J.
AU - Hoeijmakers, Jan H.J.
AU - Van Vloten, Willem A.
AU - De Gruijl, Frank R.
AU - Garssen, Johan
N1 - Funding Information:
We are grateful to Coen Molenbeek, Diane Kegler, Piet van Schaaik, and Hans Strootman from the animal facility of the National Institute of Public Health and the Environment in Bilthoven for performing many of the described experiments. We thank Ilse Bihari (Department of Dermatology, University Medical Center Utrecht) and Marjan Jongsma (Department of Dermatology, Leiden University Medical Center) for technical assistance. We are grateful also to Jan van der Linden from the department of Pulmonary Diseases, University Medical Center Utrecht, for his support in image processing of the NLDC145+ cells. The work of J.H. and G.H. was supported by the Dutch Cancer Society (Projects 98–1774, 1999–2004, and 2002–2701), the Research Institute for Diseases in the Elderly, funded by the ministry of Health, Welfare and Sports, through the Netherlands Organization for Scientific Research and an NIH program grant (AG 17242-02).
PY - 2003/10/1
Y1 - 2003/10/1
N2 - 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.
AB - 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.
KW - Contact hypersensitivity
KW - Knockout
KW - Nucleotide excision repair
KW - Skin
KW - Transgenic
UR - http://www.scopus.com/inward/record.url?scp=0141956458&partnerID=8YFLogxK
U2 - 10.1046/j.1523-1747.2003.12476.x
DO - 10.1046/j.1523-1747.2003.12476.x
M3 - Article
C2 - 14632192
AN - SCOPUS:0141956458
SN - 0022-202X
VL - 121
SP - 751
EP - 756
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 4
ER -