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(American Journal of Pathology. 2004;165:879-887.)
© 2004 American Society for Investigative Pathology

Resistance of CD1d–/– Mice to Ultraviolet-Induced Skin Cancer Is Associated with Increased Apoptosis

Yasuhiro Matsumura^*, Angus M. Moodycliffe, Dat X. Nghiem^*, Stephen E. Ullrich^* and Honnavara N. Ananthaswamy^*

From the Department of Immunology,^* The University of Texas M.D. Anderson Cancer Center, Houston, Texas; and the Department of Nutrition, Nestle Research Center, Lausanne, Switzerland

Inhibition of p53-induced epidermal apoptosis, generation of p53 mutations, and suppressor T cells are the critical events responsible for the induction and development of UV-induced skin cancers. Recently, we demonstrated that CD1d knockout mice were resistant to UV-induced immunosuppression, prompting us to further address the role of CD1d in regulating UV carcinogenesis. We, therefore, investigated the response of wild-type (WT) and CD1d–/– mice to UV carcinogenesis. We found that although 100% of WT mice developed skin tumors after 45 weeks of UV irradiation, only 60% of CD1d–/– mice developed skin tumors. Surprisingly, keratinocytes and fibroblasts from CD1d–/– mice were more sensitive to UV-induced apoptosis and persisted longer than cells derived from WT mice. In addition, epidermis and dermis taken from chronically UV-irradiated CD1d–/– mice harbored significantly fewer p53 mutations than WT mice. Our findings identify an unexpected and novel function for CD1d as a critical molecule regulating UV carcinogenesis, by inhibiting apoptosis to prevent elimination of potentially malignant keratinocytes and fibroblasts.

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