Chemokine and chemokine receptor expression analysis in target organs of acute graft-versus-host disease

Abstract

Acute graft-versus-host disease (aGVHD) is a major complication after allogeneic bone marrow transplantation (allo-BMT), and infiltration of donor leukocytes into aGVHD target organs is partially orchestrated by chemokines. Using a murine BMT model, the expression of 30 chemokines or chemokine receptors in the lung, liver, gut and tongue was analyzed using real-time PCR at 1, 2, 3 and 6 weeks after BMT during the development of clinical aGVHD and target organ histopathology. CXCL9-11 expression was linked to elevated expression of CXCR3 in the gut, lung and tongue. In contrast, hepatic CXCR3 expression was not changed, whereas a clear association was seen for CXCL16 and CXCR6 expression. An elevated intestinal CCL3 expression 1 week after allo-BMT was associated with an increased expression of CCR5 but not CCR1 or CCR3, and in the lung and liver CCL3-CCL5 expression was associated with increases in CCR1 and CCR5. Overexpression of CCL2, CCL8, CCL12 and their receptor CCR2 was found in the liver and lung, but not in the gut and tongue. On the basis of the differences in kinetics and organ distribution, more studies are required to better characterize specific targets within this network, as this will allow the development of novel preventive and therapeutic approaches by using single or multiple targeting reagents.

Early-phase GVHD gene expression profile in target versus non-target tissues: kidney, a possible target?

“…Several groups have explored and identified the role of various chemokines in T-cell migration and trafficking to target tissues in the GVHD process. 14,36,48 In line with these observations, we have found that expression levels of CXCL1, CXCL9, CXCL11 and CCL5 were increased after allo-SCT. Interestingly, whereas the expression of CXCL1 and CXCL13 was higher in the liver, CXCL9, CXCL11 and CCL5 were more highly expressed in the kidney.…”

Acute graft-versus-host disease: from the bench to the bedside

“…100 Expression of CXCR3 or CCR2 on donor CD8 ϩ T cells targets these cells to the gut and liver but not lung. [101][102][103][104] These results suggest that strategies that influence T-cell migration, particularly to GVHD target organs, may offer promise for reducing GVHD target organ-specific injury, although the redundancy of chemokines and their receptors may hinder clinical efficacy in the context of GVHD prevention or therapy. As such, targeting lymphocyte/integrin interaction may be a more promising way to explore.…”

Liver Graft versus Host Disease after Allogeneic Peripheral Stem Cell Transplantation: Update on Etiopathogenesis and Diagnosis

“…The liver expression of CCL3-CCL5 was associated with an increase of CCR1 and CCR5. The hepatic expression of CCL2, CCL8, CCL12 and their receptor CCR2 were also increased [28]. CCR5 is a CC chemokine receptor.…”