INKT cells regulate plasmacytoid dendritic cell population in bone marrow (98.16)

Abstract

Abstract Plasmacytoid dendritic cells (pDC) develop and proliferate in bone marrow and migrate to peripheral organs. pDCs produce IFNα and play a role in viral infections and autoimmune diseases. Mechanisms that regulate the development of pDC in the bone marrow are not fully understood. Invariant natural killer T (iNKT) cells comprise of a small population of lymphocytes in the bone marrow. Here, we examined the role of iNKT cells on pDC population in the bone marrow in vivo and in vitro. Bone marrow cells from wild-type, CD1d-deficient, and iNKT cell transgenic (Vα14-Tg) BALB/c mice were cultured with Flt3 ligand (FL) and αGalCer. We found that although all DCs were activated, as determined by expression of MHCII and CD86, in the presence of activated iNKT cells, the proportion of pDCs (CD11c+PDCA1+B220+) was consistently reduced in the presence of activated iNKT cells. Similar results were found in vivo, where an injection of FL and αGalCer reduced the proportion of pDCs, whereas the proportion of myeloid DCs (CD11c+CD11b+) was unchanged or slightly increased, in the bone marrow and spleen. Interestingly, FL+αGalCer increased CCR7 expression on bone marrow pDCs, but not on myeloid DCs, suggesting that iNKT cells may contribute to the egress of pDCs from the bone marrow. Such effect of FL+αGalCer injection was not seen in CD1d-deficient mice. In summary, these data suggest a role of iNKT cells in the development and homeostasis of pDCs.