CCL11 blocks IL-4 and GM-CSF signaling in hematopoietic cells and hinders dendritic cell differentiation via suppressor of cytokine signaling expression.
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.
Stevenson
Nigel J
NJ
Infection and Immunity, Cancer Research and Cell Biology, School of Biomedical Science, Queen's University of Belfast, Belfast, Northern Ireland.
Addley
Mark R
MR
Ryan
Elizabeth J
EJ
Boyd
Caroline R
CR
Carroll
Helen P
HP
Paunovic
Verica
V
Bursill
Christina A
CA
Miller
Helen C
HC
Channon
Keith M
KM
McClurg
Angela E
AE
Armstrong
Marilyn A
MA
Coulter
Wilson A
WA
Greaves
David R
DR
Johnston
James A
JA
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D054413:Chemokine CCL11 / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006413:Hematopoietic System / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D015847:Interleukin-4 / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism*
D054413:Chemokine CCL11; D016207:Cytokines; D018836:Inflammation Mediators; D043562:Receptors, G-Protein-Coupled; C108944:SOCS1 protein, human; C106644:SOCS3 protein, human; C491590:Socs1 protein, mouse; C491411:Socs3 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D019206:GTP-Binding Protein alpha Subunits, Gi-Go