Trem-1 and Ultraviolet Radiation-induced Immune Suppression

The overall goal of this study is to determine novel mechanisms for ultraviolet light (UV)-induced suppression of the immune system in human subjects and to improve understanding of UV-induced skin carcinogenesis.

Sunlight is the major environmental agent to which the skin is exposed. Injudicious exposure to wavelengths in the ultraviolet spectrum can lead to sunburn, aging of the skin, skin cancer and a variety of photosensitivity diseases, many of which have an immunologic pathogenesis. American Cancer Society acknowledges that most skin cancers are a direct result of exposure to the ultraviolet (UV) rays in sunlight. Skin cancer has also been linked to exposure to some artificial sources of UV rays (indoor tanning, welding and metal work, and phototherapy). UV, in addition to producing mutant cells, also impairs host cell-mediated immune responses that have evolved to identify and eradicate the mutant cells before they develop into clinically apparent malignancies. In fact, organ transplant recipients who are treated with immunosuppressive medications have a greatly increased risk (up to 100 times) of UV induced skin cancers and the tumors that do develop behave more aggressively. Triggering receptor expressed on myeloid cells (Trem)-1 is highly expressed by myeloid cells in human infectious and inflammatory diseases and is associated with poor prognosis of cancer patients. However, most studies have focused on Trem1 mediated effects on innate immune cells such as neutrophils in inflammatory reactions. Little is known about whether and how Trem1 regulates the adaptive immunity, especially the activity of antigen presenting cells (APC) to regulate the activation and function of antigen specific T cells. Our study will demonstrate a novel mechanism for Trem1 signaling in T cell mediated immune responses and photocarcinogenesis in skin. Different biological parameters in UV exposed skin tissues will be analyzed, which are crucial for UV-induced DNA damage, erythema, and immune suppressive effects that have been directly associated with photoimmunology and implicated in the risk of skin cancer. These will correlated with the responsiveness of allergen induced contact hypersensitivity. Participants will be stratified based on gender and then randomly assigned to: 1) Control 2) Non-UVB, or 3) UVB groups. The primary endpoint for the study will be the CHS evaluation on day 34.The Control group no DPCP (Group 1) will serve as a negative control while the UVB \& diphenylcyclopropenone (DPCP) group (Group 2) will serves as a positive control for measurement of response to irritant (contact hypersensitivity = CHS). Subjects in the UVB, DPCP, and Biopsy group (Group 3), who have no more than one standard deviation above the mean of CHS from the negative Control group, will be considered as Non-responders.