Editors' ChoiceSkin Diseases

Sensing Sun Damage

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Science Translational Medicine  15 Aug 2012:
Vol. 4, Issue 147, pp. 147ec144
DOI: 10.1126/scitranslmed.3004718

Too much fun in the sun can leave a person’s skin red and inflamed, but these conditions might just be the tip of the iceberg. In addition to sunburns, the ultraviolet B (UVB) portion of the solar radiation spectrum—which includes wavelengths between 290 and 310 nm—also drives aging and transformation of cells to a cancerous state. Through an unidentified sensor, UVB rays spur skin damage via release of proinflammatory compounds [such as tumor necrosis factor–α (TNF-α) and interleukin-6 (IL-6)] while also suppressing skin immunity. Now, Bernard et al. show that UVB exposure stimulates the innate-immune Toll-like receptor 3 (TLR3) in normal cells of the human skin epidermis (keratinocytes).

TLR3 is highly conserved from flies to mammals and senses the presence of pathogens by detecting double-stranded RNA. The authors found that normal human keratinocytes that had been exposed to UV irradiation in culture produced small nuclear RNAs, which stimulated surrounding non–UV-damaged keratinocytes and blood cells to release inflammatory mediators. By comparing the sequences of RNAs recovered from UVB-treated versus untreated human skin cells, the authors detected the release, after UVB exposure, of specific RNAs with double-stranded domains that did not encode proteins. Skin cells isolated from mice that lacked TLR3 did not release the inflammatory cytokine TNF-α in response to UVB damage. As a model for allergic and irritant skin dermatitis—or contact sensitization—the authors applied the chemical dinitrofluorobenzene to the skin of TLR3-deficient and control mice and then measured skin thickness. Normal mice exposed to UVB rays were able to limit their immune response when the contact-sensitizing agent was applied, whereas TLR3-deficient mice could not control the inflammatory response.

It remains to be determined whether UVB-induced RNA release or TLR3 up-regulation is a possible trigger for photosensitive disorders and autoimmune diseases that are worsened by sun exposure. Further study is also needed to shed light on the role of noncoding RNAs and TLR3-controlled cytokines in the progression of UV-damaged cells to skin cancer.

J. J. Bernard et al., Ultraviolet radiation damages self noncoding RNA and is detected by TLR3. Nat. Med., 8 July 2012 (10.1038/nm.2861). [PubMed]

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