Constitutive Flt3 signaling impacts conventional dendritic cell
function.
Abstract
The development of dendritic cells (DCs) depends on signaling via
FMS-like tyrosine kinase 3 (Flt3) receptor. How Flt3 signaling impacts
terminally differentiated DC function is unknown. This is important
given the increasing interest in exploiting Flt3 for vaccination and
tumor immunotherapy. Here, we examined DCs in mice harboring
constitutively activated Flt3 (Flt3-ITD). Flt3ITD/ITD mice possessed
expanded splenic DC subsets including plasmacytoid DC, conventional DC
(cDC)1, cDC2, double positive (DP) cDC1 (CD11c+ CD8+ CD11b- CD103+
CD86+), noncanonical (NC) cDC1 (CD11c+ CD8+ CD11b- CD103- CD86-) and
single positive (SP) cDC1 (CD11c+ CD8+ CD11b- CD103- CD86+). Outcomes of
constitutive Flt3 signaling differed depending on the cDC subset
examined. In comparison to wild type (WT) DCs, all Flt3ITD/ITD cDCs
displayed an altered surface phenotype with changes in costimulatory
molecules, major histocompatibility complex class I (MHC I) and II (MHC
II). Cytokine secretion patterns, antigen uptake, antigen proteolysis
and antigen presenting function differed between WT and Flt3ITD/ITD
subsets, particularly cDC2. In summary, Flt3 signaling impacts the
function of terminally differentiated cDCs with important consequences
for antigen presentation.