InsP4 negatively regulates dendritic cell cytokine secretion and migration to peripheral draining lymph nodes. (CAM1P.234)

Inositol 1,3,4,5-tetrakisphosphate (InsP4) is a novel second messenger that is critical for T and B cell development and activation. However, whether InsP4 has a similar regulatory role in dendritic cell (DC) function is not yet known. We show here that InsP4 differentially regulates ERK and Akt signaling in response to LPS activation of bone marrow derived DCs (BMDCs). InsP4 supports ERK activation but negatively regulates Akt and its down-stream signals. Interestingly, endogenous migratory DCs from InsP4 deficient mice and BMDCs migrated more efficiently to peripheral lymph nodes in vivo. InsP4 deficient BMDCs also have enhanced secretion of pro-inflammatory cytokines/chemokines and mediate stronger antigen presentation to antigen-specific T cells. Our data support an important role for InsP4 in DC migration and cytokine secretion, identifying InsP4 as a dual regulator of Akt and ERK signaling pathways that controls DC function.