Mice with a selective deletion of the CC chemokine receptors 5 or 2 are protected from dextran sodium sulfate-mediated colitis: Lack of CC chemokine receptor 5 expression results in a NK1.1+ lymphocyte-associated Th2-type immune response in the intestine

Pietro G. Andres, Paul L. Beck, Emiko Mizoguchi, Atsushi Mizoguchi, Atul K. Bhan, Tracey Dawson, William A. Kuziel, Nobuyo Maeda, Richard P. MacDermott, Daniel K. Podolsky, Hans Christian Reinecker

Research output: Contribution to journalArticle

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Abstract

The chemokine receptors CCR2 and CCR5 and their respective ligands regulate leukocyte chemotaxis and activation. To determine the role of these chemokine receptors in the regulation of the intestinal immune response, we induced colitis in CCR2- and CCR5-deficient mice by continuous oral administration of dextran sodium sulfate (DSS). Both CCR2- and CCR5-deficient mice were susceptible to DSS-induced intestinal inflammation. The lack of CCR2 or CCR5 did not reduce the DSS-induced migration of macrophages into the colonic lamina propria. However, both CCR5-deficient mice and, to a lesser degree, CCR2-deficient mice were protected from DSS-induced intestinal adhesions and mucosal ulcerations. CCR5-deficient mice were characterized by a greater relative infiltration of CD4+ and NK1.1+ lymphocyte in the colonic lamina propria when compared to wild-type and CCR2-deficient mice. In CCR5-deficient mice, mucosal mRNA expression of IL-4, IL-5, and IL-10 was increased, whereas that of IFN-γ was decreased, corresponding to a Th2 pattern of T cell activation. In CCR2-deficient mice, the infiltration of Th2-type T cells in the lamina propria was absent, but increased levels of IL-10 and decreased levels of IFN-γ may have down regulated mucosal inflammation. Our data indicate that CCR5 may be critical for the promotion of intestinal Th1-type immune responses in mice.

Original languageEnglish (US)
Pages (from-to)6303-6312
Number of pages10
JournalJournal of Immunology
Volume164
Issue number12
StatePublished - Jun 15 2000

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CCR2 Receptors
CCR5 Receptors
Dextran Sulfate
Colitis
Intestines
Lymphocytes
Mucous Membrane
Chemokine Receptors
Interleukin-10
Leukocyte Chemotaxis
Inflammation
T-Lymphocytes
Th2 Cells
Interleukin-5
Interleukin-4
Oral Administration
Macrophages
Ligands

ASJC Scopus subject areas

  • Immunology

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Mice with a selective deletion of the CC chemokine receptors 5 or 2 are protected from dextran sodium sulfate-mediated colitis : Lack of CC chemokine receptor 5 expression results in a NK1.1+ lymphocyte-associated Th2-type immune response in the intestine. / Andres, Pietro G.; Beck, Paul L.; Mizoguchi, Emiko; Mizoguchi, Atsushi; Bhan, Atul K.; Dawson, Tracey; Kuziel, William A.; Maeda, Nobuyo; MacDermott, Richard P.; Podolsky, Daniel K.; Reinecker, Hans Christian.

In: Journal of Immunology, Vol. 164, No. 12, 15.06.2000, p. 6303-6312.

Research output: Contribution to journalArticle

Andres, Pietro G. ; Beck, Paul L. ; Mizoguchi, Emiko ; Mizoguchi, Atsushi ; Bhan, Atul K. ; Dawson, Tracey ; Kuziel, William A. ; Maeda, Nobuyo ; MacDermott, Richard P. ; Podolsky, Daniel K. ; Reinecker, Hans Christian. / Mice with a selective deletion of the CC chemokine receptors 5 or 2 are protected from dextran sodium sulfate-mediated colitis : Lack of CC chemokine receptor 5 expression results in a NK1.1+ lymphocyte-associated Th2-type immune response in the intestine. In: Journal of Immunology. 2000 ; Vol. 164, No. 12. pp. 6303-6312.
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AU - Andres, Pietro G.

AU - Beck, Paul L.

AU - Mizoguchi, Emiko

AU - Mizoguchi, Atsushi

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AU - Dawson, Tracey

AU - Kuziel, William A.

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