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

The chemokine receptors CCR2 and CCR5 and their respective ligands regulate leukocyte chemotaxis and activation, To determine the role of these chemok ine receptors in the regulation of the intestinal immune response, we induc ed colitis in CCR2- acid CCR5-deficient mice by continuous oral administrat ion of dextran sodium sulfate (DSS). Both CCR2- and CCR5-deficient mice wer e susceptible to DSS-induced intestinal inflammation, The lack of CCR2 or C CR5 did not reduce the DSS-induced migration of macrophages into the coloni c 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 greate r relative infiltration of CD4(+) and NK1.1(+) lymphocyte in the colonic la mina propria when compared to wild-type and CCR2-deficient mice. In CCR5-de ficient mice, mucosal mRNA expression of IL-4, IL-5, and IL-IO was increase d, whereas that of IFN-gamma 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-gamma may have down regulated mucosal inflammation , Our data indicate that CCR5 may be critical for the promotion of intestin al Th1-type immune responses in mice.