CCR6-deficient mice have impaired leukocyte homeostasis and altered contact hypersensitivity and delayed-type hypersensitivity responses
Rosa Varona, … , Carlos Martínez-A., Gabriel Márquez
Rosa Varona, … , Carlos Martínez-A., Gabriel Márquez
Published March 15, 2001
Citation Information: J Clin Invest. 2001;107(6):R37-R45. https://doi.org/10.1172/JCI11297.
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CCR6-deficient mice have impaired leukocyte homeostasis and altered contact hypersensitivity and delayed-type hypersensitivity responses

Abstract

CCR6 expression in dendritic, T, and B cells suggests that this β-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.

Authors

Rosa Varona, Ricardo Villares, Laura Carramolino, Íñigo Goya, Ángel Zaballos, Julio Gutiérrez, Miguel Torres, Carlos Martínez-A., Gabriel Márquez

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Figure 1

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Targeted disruption of the CCR6 gene. (a) Targeting strategy. CCR6 WT lo...
Targeted disruption of the CCR6 gene. (a) Targeting strategy. CCR6 WT locus with partial restriction map. The coding sequence (CDS), neomycin resistance gene (Neo), and thymidine kinase gene (TK) are shown as open, filled, and shaded boxes, respectively. A thick filled bar shows probe A, used in Southern blot analysis for screening genomic DNA. Arrows mark the position and direction of synthesis of oligonucleotides used in PCR genotyping. B, BamHI; P, PstI; H, HindIII; E, EcoRI; S, SmaI; X, XbaI; N, NotI; K, KpnI; O, XhoI. (b) Representative Southern blot analysis of BamHI-digested tail DNA from WT (+/+), heterozygous (+/–), and homozygous (–/–) CCR6 mice using probe A. Band sizes in kilobases for the WT and knockout alleles are indicated on the left. (c) Representative Northern blot analysis of the CCR6 mRNA expression in thymus and spleen from CCR6 WT (+/+) and knockout (–/–) animals. The size of the CCR6 transcript in kilobases is indicated on the left.