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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Altered response of CCR6–/– mice in contact hypersensitivity inflammatio...
Altered response of CCR6–/– mice in contact hypersensitivity inflammation. (a) CCR6–/– (n = 12; circles) and CCR6+/+ (n = 12; squares) mice were sensitized by epicutaneous application of 25 μl of 0.5% DNFB solution on the shaved abdomen. Increases in ear swelling were measured 24, 48, and 72 hours after challenge with 20 μl of 0.2% DNFB on the ears. Individual data and the mean value for each group are presented. Two-tailed t-test values for DNFB data: P = 0.006 (24 hours), P = 0.005 (48 hours), P = 0.002 (72 hours). (b) Similar number of lymph node cells in CCR6+/+ and CCR6–/– mice. Animals were sensitized with DNFB (filled bars) or left untreated (open bars); 5 days later, lymphocytes from IAB (I+A+B) LNs were prepared and counted. (c) CCR6–/– lymphocytes proliferate in response to specific and nonspecific stimuli. CCR6–/– and CCR6+/+ animals were sensitized with DNFB (filled symbols) or untreated (open symbols); 5 days later, cells from draining (I+A+B) or control mesenteric LNs were recovered and cultured for 36 hours alone or in the presence of DNBS, as indicated. Cultures were pulsed with 3H-thymidine for 18 hours, and cell proliferation was estimated. Similar experiments were performed to measure in vitro responses to a polyclonal stimulus, Con A. Each value represents the average of three separate groups, consisting of pooled LNs from two mice. All assays were performed in triplicate.