Differential role of UVB-induced photolesions in skin and immune response.
JOURNAL OF IMMUNOLOGY(2011)
摘要
UV-induced DNA damage is an essential step in the process by which UVB can alter host resistance to infections diseases. UV-light induces two types of photolesion on DNA that are repaired by photolyases (absent in placental mammals) or Nucleotide Excision Repair. Photolyases are capable of repair these lesions using a photon of light as source of energy. Although the deleterious effects of UV are widely known, the specific role of each photolesion in the induction of changes in the immune response remains unknown. It has been shown in vivo that CPDs are responsible for the majority of the effects after UVB skin irradiation of DNA repair proficient mice, such as erythema, apoptosis, hyperplasia, tumorigenesis and immunosuppression. However the role of 6-4PP is still unknown. We show that the removal of CPD lesions prevents hyperplasia and induces dark skin pigmentation. When 6-4PPs were removed, UVB promoted hyperplasia and tanning. Also, unlike 6-4PP removal, CPD removal is capable of preventing the development of p53 epidermal patches, which have a direct correlation with carcinoma development. Furthermore, the CPD removal is sufficient to suppress the induction of Treg (CD4+CD25+Foxp3) in draining lymph nodes and spleen indicating a minor state of immunosuppression. This study can provide new information as how immune responses are regulated depending of the lesion that is repaired and improve our understanding the immune system role in skin cancer induction.
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关键词
immune response,photolesions,skin,uvb-induced
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