UV has the unusual ability to cause immunosuppression by recruiting T regulatory cells (T regs). UV has thus been used to treat autoimmune conditions of the skin, such as psoriasis, but there has been no real understanding of how UV-treated skin manages to attract T regs and eliminate the inflammation.
T reg proliferation and peripheral expansion requires cues from activated mature DCs, which express several receptors including receptor-activated NF-κB (RANK). The authors now show that RANK's ligand, RANKL, is expressed by skin cells (keratinocytes) that have been exposed to UV. The DCs in the UV-treated area are probably activated through their interaction with the keratinocytes, and this helps them recruit T regs.
DCs from transgenic mice overexpressing RANKL supported T reg proliferation both in vitro and in vivo. The transgenic mice had 2–3 times as many T regs as normal mice and 6 times as many T regs as mice lacking RANKL. It is not yet clear how RANKL expression specifically attracts benign T regs without also alerting inflammatory CD8+ T cells. Nonetheless, Beissert speculates that a topical RANKL application might provide some relief for patients with inflammatory skin disorders, such as psoriasis or eczema.