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

Abstract

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 CCL11induces suppressor of cytokine signaling (SOCS)1and 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 STAT6activation in a range of hematopoietic cells. This blockade of cytokine signaling by CCL11 results inreduced differentiation and endocytic ability ofDCs, implicating CCL11-induced SOCS as media-tors of chemotactic inflammatory control. These findings demonstrate cross-talk between chemo-kine 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.