Essential role of CCR6 in directing activated T cells to the skin during contact hypersensitivity.
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-gamma 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.
Paradis
Timothy J
TJ
Department of Immunology, Pfizer Global Research and Development, Groton, Connecticut 06340, USA. Timothy.J.Paradis@.Pfizer.com
Cole
Susan H
SH
Nelson
Robin T
RT
Gladue
Ronald P
RP
D000276:Adjuvants, Immunologic / Q000633:toxicity; D019264:Adoptive Transfer; D000818:Animals; D002465:Cell Movement / Q000276:immunology; D003877:Dermatitis, Contact / Q000276:immunology* / Q000473:pathology*; D015870:Gene Expression / Q000276:immunology; D006241:Haptens / Q000494:pharmacology; D007371:Interferon-gamma / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010081:Oxazolone / Q000633:toxicity; D054399:Receptors, CCR6 / Q000235:genetics* / Q000276:immunology*; D013601:T-Lymphocytes / Q000473:pathology*
D000276:Adjuvants, Immunologic; C498126:CCR6 protein, mouse; D006241:Haptens; D054399:Receptors, CCR6; D010081:Oxazolone; D007371:Interferon-gamma