Down-regulation of the beta-chemokine receptor CCR6 in dendritic cells mediated by TNF-alpha and IL-4.
Chemokines are involved in the control of dendritic cell (DC) trafficking, which is critical for the immune response. We have generated DC from human umbilical cord blood CD34+ progenitors cultured with granulocyte-macrophage colony-stimulating factor, tumor necrosis factor alpha (TNF-alpha), and stem cell factor. Using an anti-CCR6 monoclonal antibody, we observed that these cells showed maximum expression of this beta-chemokine receptor when they were immature, as determined by their relatively low expression of several DC maturation markers such as CD1a, CD11c, CD14, CD40, CD80, and CD83. Immature DC responded strongly to macrophage inflammatory protein-3alpha (MIP-3alpha), the CCR6 ligand, in migration and calcium mobilization assays. CCR6 expression decreased in parallel with the DC maturation induced by prolonged TNF-alphaq treatments. Interleukin-4 was also able to decrease CCR6 protein levels. Our findings suggest that the MIP-3alpha/CCR6 interaction plays an important role in the trafficking of immature DC to chemokine production sites such as injured or inflamed peripheral tissues, where DC undergo maturation on contact with antigens.
Carramolino
L
L
Departamento de Inmunología y Oncología, Centro Nacional de Biotecnología, UAM, Madrid, Spain.
Kremer
L
L
Goya
I
I
Varona
R
R
Buesa
J M
JM
Gutiérrez
J
J
Zaballos
A
A
Martínez-A
C
C
Márquez
G
G
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis; D002460:Cell Line; D054418:Chemokine CCL20; D019742:Chemokines, CC / Q000378:metabolism / Q000494:pharmacology; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism*; D015536:Down-Regulation; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism* / Q000494:pharmacology; D019402:Macrophage Inflammatory Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D054399:Receptors, CCR6; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000235:genetics; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D018411:Spodoptera / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology
D000911:Antibodies, Monoclonal; C108355:CCL20 protein, human; C106311:CCR6 protein, human; D054418:Chemokine CCL20; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins; D054399:Receptors, CCR6; D019707:Receptors, Chemokine; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4