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Identification of the molecular target for the suppression of contact hypersensitivity by ultraviolet radiation
L A Applegate1, R D Ley, J Alcalay
1University of Texas, M. D. Anderson Cancer Center, Department of Immunology, Houston, Texas 77030.
Abstract:
This study was conducted to explore the involvement of DNA damage in the suppression of contact hypersensitivity (CHS) by UV irradiation. The opossum, Monodelphis domestica, was used because cells of these marsupials have an enzyme that is activated by visible light (photoreactivating enzyme) and repairs ultraviolet radiation (UVR)-induced pyrimidine dimers in DNA. A single dose of 1,500 J/m2 of UVB (280-320 nm) radiation, representing 2 minimal erythema doses, was administered to the dorsal skin of opossums. This treatment prevented the opossums from developing a CHS response to dinitrofluorobenze (DNFB) applied either at the site of irradiation or an unirradiated site. In addition, this dose of UVR decreased the number of ATPase+ epidermal Langerhans cells in the dorsal epidermis to approximately 3% of that in unirradiated skin at the time of DNFB application. Treatment of the animals with wavelengths that activate the repair enzyme (320-500 nm, photoreactivating light, PRL) for 120 min immediately after UV irradiation inhibited the UVR-induced suppression of CHS almost completely. Exposure to PRL before UVR did not prevent UVR-induced suppression of CHS. PRL treatment after UV irradiation also prevented the decrease in the number of ATPase+ Langerhans cells. Measurements of lesions in DNA indicated that PRL treatment removed around 85% of the UVR-induced pyrimidine dimers. These data provide direct evidence that DNA, and most likely, the pyrimidine dimer, is the primary molecular target for the UVB-induced suppression of contact hypersensitivity to haptens applied to irradiated or unexposed skin.
Insights
Ultraviolet (UV) irradiation suppresses contact hypersensitivity (CHS) by damaging DNA. Repairing UV-induced DNA damage with photoreactivating light (PRL) almost completely prevents this suppression, indicating DNA is the primary target.
Area of Science:
- Immunology
- Photobiology
- Dermatology
Background:
- Ultraviolet (UV) irradiation is known to suppress the skin's immune response, a phenomenon called contact hypersensitivity (CHS).
- The precise molecular mechanisms underlying UV-induced immune suppression are not fully understood.
- Marsupials like the opossum possess a photoreactivating enzyme that repairs DNA damage caused by UV radiation.
Purpose of the Study:
- To investigate the role of DNA damage in UV-induced suppression of contact hypersensitivity (CHS).
- To determine if repairing DNA damage can reverse the immunosuppressive effects of UV radiation on CHS.
Main Methods:
- Opossums received UVB irradiation, followed by either photoreactivating light (PRL) or no treatment.
- Contact hypersensitivity was induced using dinitrofluorobenzene (DNFB) at irradiated and unirradiated sites.
- Changes in epidermal Langerhans cells and DNA lesions (pyrimidine dimers) were quantified.
Main Results:
- UVB irradiation suppressed CHS and reduced Langerhans cells, regardless of DNFB application site.
- Post-UVB treatment with PRL almost completely inhibited CHS suppression and prevented Langerhans cell depletion.
- PRL treatment removed approximately 85% of UV-induced pyrimidine dimers in DNA.
Conclusions:
- DNA damage, specifically pyrimidine dimers, is the primary molecular target responsible for UV-induced suppression of CHS.
- Photoreactivation therapy targeting DNA repair can effectively counteract UV-induced immune suppression in the skin.
- These findings highlight the critical role of DNA integrity in maintaining immune responses following UV exposure.