Langerhans Cells and Cytokines in UV-irradiated Melanocytic Nevi

Kim, Do Hyeong; Choi, Kyu Cherl; Chung, Byoung Soo

Abstract

BACKGROUND: It is well established that UV-induced DNA damage is involved in the mutation of oncogenes and tumor suppressor genes, and the subsequent development of skin cancers. Langerhans cells (LC) are thought to play an important role in the presentation of tumor antigens for the induction of anti-tumor immunity. Cytokines may have a key role in the UV-induced modulation of the skin's immune system.
OBJECTIVE
To clarify the role of Langerhans cells, cytokines in UV-irradiated Melanocytic Nevi vs non-irradiated melanocytic nevi.
METHODS
Skin biopsies from 10 melanocytic nevi, taken from partially covered melanocytic navi and irradiated part with a defined UV dose, were examined. Immunohistochemical staining was used for the quantitative distribution of LC and the expression of cytokines which are related to LC migration and maturation (TNF-alpha and GM-CSF), Th1 response (IL-12), and Th2 response (IL-10).
RESULTS
LC number increased in non-irradiated neoplastic epithelium compared to control skin. In UV-exposed nevi, LC density decreased significantly but a constant number was still maintained. TNF-alpha and GM-CSF were predominently expressed in lesional epithelium and some nevus cells, 2 days after irradiation. GM-CSF expression in nevus cells was maintained up to 7 days after exposure. IL-10 was expressed in epidermis 2 days after exposure. While IL-12 was weakly positive and maintained up to 7 days in unexposed lesional epidermis, it was not detected after 2 days but reappeared in an exposed lesion after 7 days.
CONCLUSION
Langerhans cells (LC) modulated by cytokines in UV-exposed skin may have a functional role in UV-induced carcinogenesis.