Narrow band ultraviolet B (NB-UVB) and Broad band ultraviolet B (BB-UVB) are commonly used for the treatment of Atopic Dermatitis (AD) among others, and has been shown by us and others to trigger LINE-1 reactivation in human keratinocytes. LINE-1 constitutes ~17% of human genome, has played important evolutionary role, and its reactivation may result in deleterious effects leading to DNA damage, cellular senescence and photoaging. We established a model of NB-UVB or BB-UVB irradiation on keratinocytes, and showed that these induced an increase in LINE-1 expression. Moreover, we were able to observe that the repetition of this irradiation, and thus long terme LINE-1 overexpression, induced an increase of senescence markers, double strand breaks, and a decrease in cell proliferation. On the other hand, we found that some small RNAs, able to target LINE-1 in silico, are decreased in our UV irradiation model, compared to the control. Thus, by identifying the small RNAs involved in LINE-1 regulation, deregulated in response to UV in keratinocytes, we will be able to better characterize the mechanisms involved during irradiation, and attempt to remedy them. The impact of the restoration of an adequate level of these regulatory small RNAs will be evaluated on the LINE-1 expression, as well as on cellular senescence markers, and genomic instability and photoaging. Ultimately, we would like to correlate our results with those of patients with AD treated with UV. Furthermore, by confirming our results in AD patient samples, we will help to understand the potential impact of UVB on cellular senescence and photoaging, and we will correlate our results with treatments of skin inflammation with new biological parameters (e.g., ointment containing the microRNA(s) of interest), which will prevent or reduce L1 activation.

ESDR405 - Understanding the biologic regulation and impact of Long Interspersed Nuclear Element (LINE-1) retrotransposon reactivation in keratinocytes undergoing phototherapy treatments.

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.