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Skin-based immunity

Immunosuppression results when RANKL (right) triggers production of T regs (right half of panels). BEISSERT/MACMILLAN

When skin cells are hit by a blast of UV light, they instruct dendritic cells (DCs) to suppress immunity system-wide, say Karin Loser, Stefan Beissert (University of Münster, Münster, Germany), and colleagues.

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-B (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.

Reference:

Loser, K., et al. 2006. Nat. Med. 12:1372–1379.[Medline]

Hema Bashyam

hbashyam{at}rockefeller.edu

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This Article Full Text (PDF, 910K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Bashyam, H. Search for Related Content PubMed Articles by Bashyam, H. Social Bookmarking                            What's this?