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/ITDmice 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.