CCR6-deficient mice have impaired leukocyte homeostasis and altered contact hypersensitivity and delayed-type hypersensitivity responses.
CCR6 expression in dendritic, T, and B cells suggests that this beta-chemokine receptor may regulate the migration and recruitment of antigen-presenting and immunocompetent cells during inflammatory and immunological responses. Here we demonstrate that CCR6-/- mice have underdeveloped Peyer's patches, in which the myeloid CD11b+ CD11c+ dendritic-cell subset is not present in the subepithelial dome. CCR6-/- mice also have increased numbers in T-cell subpopulations within the intestinal mucosa. In 2,4-dinitrofluorobenzene-induced contact hypersensitivity (CHS) studies, CCR6-/- mice developed more severe and more persistent inflammation than wild-type (WT) animals. Conversely, in a delayed-type hypersensitivity (DTH) model induced with allogeneic splenocytes, CCR6-/- mice developed no inflammatory response. The altered responses seen in the CHS and DTH assays suggest the existence of a defect in the activation and/or migration of the CD4(+) T-cell subsets that downregulate or elicit the inflammation response, respectively. These findings underscore the role of CCR6 in cutaneous and intestinal immunity and the utility of CCR6-/- mice as a model to study pathologies in these tissues. This article was published online in advance of the print edition. The date of publication is available from the JCI website, http://www.jci.org.
Varona
R
R
Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain.
Villares
R
R
Carramolino
L
L
Goya
I
I
Zaballos
A
A
Gutiérrez
J
J
Torres
M
M
Martínez-A
C
C
Márquez
G
G
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002465:Cell Movement; D003877:Dermatitis, Contact / Q000235:genetics* / Q000276:immunology*; D005260:Female; D006706:Homeostasis; D006968:Hypersensitivity, Delayed / Q000235:genetics* / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology; D007801:Langerhans Cells / Q000276:immunology; D007962:Leukocytes / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010581:Peyer's Patches / Q000276:immunology / Q000473:pathology; D054399:Receptors, CCR6; D019707:Receptors, Chemokine / Q000172:deficiency* / Q000235:genetics / Q000502:physiology
C106311:CCR6 protein, human; D054399:Receptors, CCR6; D019707:Receptors, Chemokine