Mice Lacking Expression of Secondary Lymphoid Organ Chemokine Have Defects in Lymphocyte Homing and Dendritic Cell Localization

Gunn, Michael D.; Kyuwa, Shigeru; Tam, Carmen; Kakiuchi, Terutaka; Matsuzawa, Akio; Williams, Lewis T.; Nakano, Hideki

Additional support for our conclusion that SLC is involved in DC homing to T cell zones comes from recent studies of chemokine receptor expression by DCs in vitro (47) (48) (49) . DCs derived in culture from monocytes or CD34 Ï© precursors do not express CCR7, the receptor for SLC and ELC. CCR7 expression is induced in these cells by activation with LPS, CD40 ligand, or TNF. Similarly, activated DCs increase intracellular calcium and undergo chemotaxis in response to ELC. These results suggest that immature DCs become responsive to SLC and ELC upon activation in vivo and that one or both of these chemokines is involved in the migration of activated DCs. It has been suggested that it is the activation-induced downregulation of chemokine receptors such as CCR1, CCR5, and CCR6 that allows DCs to leave sites of inflammation, whereas the more gradual induction of CCR7 on these cells allows them to enter T cell zones in response to ELC (47, 48) . Our results support this hypothesis, though we would suggest that SLC, rather than ELC, may play the predominant role.