¹Department of Immunology, Pfizer Global Research and Development, Groton, Connecticut, USA

Correspondence: Timothy J. Paradis, Department of Immunology, Pfizer Global Research and Development, MS 8220-2413, Eastern Point Road, Groton, Connecticut 06340, USA. E-mail: Timothy.J.Paradis@.Pfizer.com

Received 21 March 2007; Revised 7 June 2007; Accepted 11 July 2007; Published online 20 September 2007.

Abstract

CCR6 is expressed in a number of dermatological inflammatory diseases. Here, we report that mice sensitized with the hapten oxazolone had increased numbers of CCR6⁺ T cells in the draining lymph nodes. Using CCR6^-/- mice, we assessed the role of CCR6 on the development of contact hypersensitivity. After hapten sensitization and re-challenge, ear swelling in CCR6^-/- animals was reduced 80% as compared with wild-type (WT) control mice. This decreased level of inflammation was not related to an inhibition in T-cell activation, because CCR6^-/- lymph node cells from sensitized mice produced threefold higher levels of IFN- in culture than cells from sensitized WT mice and, when these cells were directly injected into the site of hapten challenge, induced a robust inflammatory response. However, intravenous injection of CCR6^-/- lymph node cells from sensitized mice were unable to prime naive mice to re-challenge whereas cells from primed WT mice were able to sensitize animals. These results suggest that CCR6 plays an important role in directing the trafficking of activated T cells into the skin and suggests that a CCR6 antagonist could be useful to treat skin-mediated inflammatory reactions.