Anti-CCL7 polyclonal antibody

The inflammatory response to the colonic pathogen Clostridium difficile is characterized by the induction of inflammatory cytokines including Interleukin-23 (IL-23) and interferon- (IFN-) and the recruitment of myeloid cells including Ly6C(High) monocytes. IL-23 knockout mice showed reduced expression of the monocyte chemokines Ccl4 and Ccl7, but not Ccl2, as well as reduced Ly6C(High) Ly6G(Mid) monocyte recruitment to the colon in response to C. difficile colitis. Clostridium difficile-infected CCR2(-/-) (CCR2 KO) mice showed a significant defect in Ly6C(High) Ly6G(Mid) monocyte recruitment to the colon in response to C. difficile. Although there was no decrease in expression of the inflammatory cytokines Il1b, Il6 or Tnf or reduction in the severity of colonic histopathology associated with ablation of monocyte recruitment, Slpi and Inos expression was significantly reduced in the colons of these animals. Additionally, neutralization of IFN- through the administration of anti-IFN- monoclonal antibody resulted in a significant reduction in the expression of the IFN--inducible chemokines Cxcl9 and Cxcl10, but not a reduction in the neutrophil chemokines Cxcl1, Cxcl2 and Ccl3 or the monocyte chemokine Ccl2. Consistently, monocyte and neutrophil recruitment were unchanged following anti-IFN- treatment. Additionally, Inos and Slpi expression were unchanged following anti-IFN- treatment, suggesting that Inos and Slpi regulation is independent of IFN- during C. difficile colitis. Taken together, these data strongly suggest that IL-23 and CCR2 signalling are required for monocyte recruitment during C. difficile colitis. Additionally, these studies also suggest that monocytes, but not IFN-, are necessary for full expression of Inos and Slpi in the colon.

One of the defining features of the majority of FOXP3(+) Tregs is their inability to produce typical T-cell-derived cytokines. Little is known, however, about their capacity to produce chemokines. As Tregs are constitutively present in, and rapidly traffic to, non-lympoid tissues, we hypothesized that they may produce chemokines to direct the composition of cells that infiltrate inflamed tissues. Surprisingly, we found that Tregs produce high amounts of CXCL8 (IL-8), a potent neutrophil chemoattractant. Tregs also produced other CC and CXC family chemokines, including CCL2-5, CCL7, and CXCL10. Whereas ectopic expression of FOXP3 suppressed cytokine production, it significantly induced CXCL8. Moreover, supernatants from Tregs attracted neutrophils via a CXCL8-dependent mechanism. These data provide the first evidence that although classical Tregs are defined by their lack of proinflammatory cytokine production, they secrete significant quantities of chemokines and thus may have an unappreciated role in directing the recruitment of immune cells.