Modulation of MHC class II transport and lysosome distribution by macrophage-colony stimulating factor in human dendritic cells derived from monocytes

The macrophage-colony stimulating factor (M-CSF) has been already shown to affect the function of dendritic cells (DC), Therefore, the differentiation of dendritic cells into macrophages (M Phi) might represent a pathway whic h could inhibit the immune response initiated by DC. Because Major Histocom patibility Complex class II molecules (MHC-II) are crucial for DC function, we asked whether M-CSF may influence the intracellular transport of MHC-II in monocyte derived DC, We found that, at early stages, M-CSF induced firs t a rapid redistribution of MHC-II from the MHC-II containing compartments (MIIC) to the plasma membrane and second an increase in MHC-II synthesis as observed with LPS or TNF-alpha. These processes were associated with the s orting of MHC-II from lysosomal membranes which underwent a drastic structu ral reorganization. However, in contrast to tumor necrosis factor (TNF)-alp ha or lipopolysaccharide (LPS), M-CSF neither potentiated the allostimulato ry function of DC nor allowed the stabilization of MHC-II at the cell surfa ce, but rather increased MHC-II turnover. We conclude that the rapid modula tion of MHC-II transport and distribution may participate in the inhibitory effect of M-CSF on DC function and differentiation.