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Ultraviolet radiation-induced suppression of natural killer cell activity is enhanced in xeroderma pigmentosum group
H Miyauchi-Hashimoto1, H Okamoto, K Tanaka
1Department of Dermatology, Kansai Medical University, Moriguchi, Osaka, Japan.
Abstract:
Xeroderma pigmentosum group A gene-deficient mice easily develop skin cancers by ultraviolet radiation. Natural killer cells play an important part in tumor surveillance. To study whether ultraviolet radiation-induced suppression of natural killer cell function is involved in the high incidence of skin tumors in patients with xeroderma pigmentosum, we analyzed the number and activity of natural killer cells in ultraviolet B-irradiated xeroderma pigmentosum A model mice. The number of natural killer cells in peripheral blood significantly decreased after ultraviolet B-irradiation only in xeroderma pigmentosum A mice, but those in the spleen were not affected. As compared with the wild-type mice, the xeroderma pigmentosum A mice displayed a higher level of spontaneous splenic natural killer cell activity (10%-15% vs 3%) and inducible natural killer activity (30%-50% vs 20%-25%) after injection of polyinosinic:polycytidylic acid. At 24 h after the last irradiation of three and five daily consecutive exposures to 500 mJ per cm2-ultraviolet B, however, the natural killer activity in xeroderma pigmentosum A mice decreased to 60 and 30% of the preirradiated level, respectively, but it did not in the wild-type mice. The depression of natural killer activity in xeroderma pigmentosum A mice recovered to a normal level at 10 and 15 d after the last irradiation, respectively. The high incidence of skin cancers in xeroderma pigmentosum patients may be mainly due to a defect in the repair of ultraviolet-damaged DNA of cutaneous cells, and possibly also due to an intensified ultraviolet-induced immunosuppression. Moreover, the present study suggests that the enhanced ultraviolet-induced impairment of natural killer function could be partially involved in cancer development.
Insights
Xeroderma pigmentosum A mice show reduced natural killer cell activity after ultraviolet B exposure, suggesting a role in skin cancer development. This impairment may contribute to increased cancer risk in patients with this genetic disorder.
Area of Science:
- Immunology
- Dermatology
- Genetics
Background:
- Xeroderma pigmentosum (XP) is a genetic disorder characterized by extreme sensitivity to ultraviolet (UV) radiation and a high incidence of skin cancers.
- Natural killer (NK) cells are crucial immune cells involved in tumor surveillance and elimination.
- UV radiation is known to suppress immune function, potentially contributing to cancer development.
Purpose of the Study:
- To investigate the role of NK cell function in UV radiation-induced skin cancer development in a mouse model of Xeroderma pigmentosum group A (XPA).
- To determine if UV radiation-induced suppression of NK cell activity is enhanced in XPA mice compared to wild-type mice.
Main Methods:
- Analysis of NK cell numbers and activity in peripheral blood and spleen of UV B-irradiated XPA mice and wild-type controls.
- Assessment of spontaneous and inducible NK cell activity following polyinosinic:polycytidylic acid injection.
- Evaluation of NK cell activity recovery after multiple UV B exposures.
Main Results:
- UV B irradiation significantly decreased peripheral blood NK cell numbers in XPA mice, but not in wild-type mice.
- XPA mice exhibited higher spontaneous and inducible splenic NK cell activity compared to wild-type mice prior to irradiation.
- UV B irradiation caused a marked, dose-dependent decrease in NK cell activity in XPA mice, which recovered over 10-15 days, unlike in wild-type mice.
Conclusions:
- The high incidence of skin cancer in XP patients may be attributed to defective DNA repair and potentially intensified UV-induced immunosuppression.
- Enhanced UV-induced impairment of NK cell function in XPA mice could be a contributing factor to cancer development.
- NK cell dysfunction warrants further investigation as a potential therapeutic target in XP.