CCL11 blocks IL-4 and GM-CSF signaling in hematopoietic cells and hinders dendritic cell differentiation via suppressor of cytokine signaling expression.

Journal article

The chemokine eotaxin/CCL11 is an important mediator of leukocyte migration, but its effect on inflammatory cytokine signaling has not been explored. In this study, we find that CCL11 induces suppressor of cytokine signaling (SOCS)1 and SOCS3 expression in murine macrophages, human monocytes, and dendritic cells (DCs). We also discover that CCL11 inhibits GM-CSF-mediated STAT5 activation and IL-4-induced STAT6 activation in a range of hematopoietic cells. This blockade of cytokine signaling by CCL11 results in reduced differentiation and endocytic ability of DCs, implicating CCL11-induced SOCS as mediators of chemotactic inflammatory control. These findings demonstrate cross-talk between chemokine and cytokine responses, suggesting that myeloid cells tracking to the inflammatory site do not differentiate in the presence of this chemokine, revealing another role for SOCS in inflammatory regulation.

Authors: Stevenson, N; Addley, MR; Ryan, E; Boyd, C; Carroll, H

• Publication status: Published
• Journal: Journal of leukocyte biology
• Volume: 85
• Issue: 2
• Pages: 289-297
• Publication date: 2009-02-01
• DOI: 10.1189/jlb.0708394
• EISSN: 1938-3673
• ISSN: 0741-5400
• Language: English
• Keywords: Interleukin-4; Macrophages; Suppressor of Cytokine Signaling Proteins; Cytokines; Endocytosis; Animals; Granulocyte-Macrophage Colony-Stimulating Factor; Dendritic Cells; Signal Transduction; Inflammation Mediators; Mice, Inbred C57BL; Cell Line; Humans; Chemokine CCL11; Receptors, G-Protein-Coupled; Cell Differentiation; Hematopoietic System; Mice; GTP-Binding Protein alpha Subunits, Gi-Go