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-macropha ge colony-stimulating factor, tumor necrosis factor alpha (TNF-alpha), and stent 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 se veral DC maturation markers such as CD1a, CD11c, CD14, CD40, CD80, and CD83 , Immature DC responded strongly to macrophage inflammatory protein-3 alpha (MIP-3 alpha), the CCR6 ligand, in migration and calcium mobilization assa ys, CCR6 expression decreased iu parallel with the DC maturation induced by prolonged TNF-alpha treatments, Interleukin-4 was also able to decrease CC R6 protein levels. Our findings suggest that the MIP-3 alpha/CCR6 interacti on plays an important role in the trafficking of immature DC to chemokine p roduction sites such as injured or inflamed peripheral tissues, where DC un dergo maturation on contact with antigens.