CCL27/PESKY: a novel paradigm for chemokine function.

Chemokines play a central role in regulating leukocyte migration. The recently discovered CC chemokine ligand 27 (CCL27), through interaction with its cognate receptor, CC chemokine receptor 10 (CCR10), appears to be involved in attracting a subset of memory T cells to the skin during some cutaneous inflammatory responses. Strangely, CCL27 can also be produced as a non-secreted form, as a result of alternative splicing. This protein, termed PESKY, is targeted to the nucleus where it is able to modulate transcription and alter cell morphology. Specifically, PESKY induces a rearrangement of the actin cytoskeleton, manifest by the disruption of stress fibres. This consequently enhances cell motility. Surprisingly, secreted CCL27 can also reach the nucleus after CCR10-mediated internalisation, where it may also be capable of directly modulating transcription to alter cell behaviour. This review will discuss these unprecedented findings.