Please use this identifier to cite or link to this item: https://doi.org/10.1038/srep30802
Title: Highly specific blockade of CCR5 inhibits leukocyte trafficking and reduces mucosal inflammation in murine colitis
Authors: Mencarelli, A 
Cipriani, S
Francisci, D
Santucci, L
Baldelli, F
Distrutti, E
Fiorucci, S
Keywords: CD11b antigen
chemokine
cyclohexane derivative
dextran sulfate
homeodomain protein
maraviroc
RAG-1 protein
RANTES
triazole derivative
trinitrobenzenesulfonic acid
animal
antagonists and inhibitors
C57BL mouse
CD4+ T lymphocyte
chemically induced
colitis
colon
cytology
disease model
drug effects
genetics
immunology
inflammation
intestine mucosa
knockout mouse
leukocyte
metabolism
mouse
pathology
physiology
Th17 cell
transplantation
upregulation
Animals
CD11b Antigen
CD4-Positive T-Lymphocytes
Chemokine CCL5
Chemokines
Colitis
Colon
Cyclohexanes
Dextran Sulfate
Disease Models, Animal
Homeodomain Proteins
Inflammation
Intestinal Mucosa
Leukocytes
Mice
Mice, Inbred C57BL
Mice, Knockout
Th17 Cells
Triazoles
Trinitrobenzenesulfonic Acid
Up-Regulation
Issue Date: 2016
Publisher: Nature Publishing Group
Citation: Mencarelli, A, Cipriani, S, Francisci, D, Santucci, L, Baldelli, F, Distrutti, E, Fiorucci, S (2016). Highly specific blockade of CCR5 inhibits leukocyte trafficking and reduces mucosal inflammation in murine colitis. Scientific Reports 6 : 30802. ScholarBank@NUS Repository. https://doi.org/10.1038/srep30802
Rights: Attribution 4.0 International
Abstract: Targeted disruption of leukocyte trafficking to the gut represents a promising approach for the treatment of inflammatory bowel diseases (IBDs). CCR5, the shared receptor for MIP1? and ? and RANTES, is expressed by multiple leukocytes. Here, we aimed to determine the role of CCR5 in mediating leukocyte trafficking in models of colitis, and evaluate the therapeutic potential of maraviroc, an orally active CCR5 antagonist used in the treatment of CCR5-tropic HIV. Acute and chronic colitis were induced by administration of DSS or TNBS to wild-type and CCR5-/-' mice or adoptive transfer of splenic naïve CD4 + T-cells from wild type or CCR5-/-' mice into RAG-1-/-'. CCR5 gene ablation reduced the mucosal recruitment and activation of CCR5-bearing CD4+ and CD11b+ leukocytes, resulting in profound attenuation of signs and symptoms of inflammation in the TNBS and transfer models of colitis. In the DSS/TNBS colitis and in the transfer model, maraviroc attenuated development of intestinal inflammation by selectively reducing the recruitment of CCR5 bearing leukocytes. In summary, CCR5 regulates recruitment of blood leukocytes into the colon indicating that targeting CCR5 may offer therapeutic options in IBDs.
Source Title: Scientific Reports
URI: https://scholarbank.nus.edu.sg/handle/10635/182439
ISSN: 2045-2322
DOI: 10.1038/srep30802
Rights: Attribution 4.0 International
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