Identification, phenotype, migration, and function of c-kit-expressing dendritic cells in vivo (91.12)

Abstract

Abstract We previously reported c-kit induction on total lung DCs by in vitro treatment with Th2/Th17- (ovalbumin plus cholera toxin; OVA/CT) but not Th1-inducing (CpG) factors. Furthermore, we showed that c-kit plays a contributory role to Th2, and in particular to Th17, immune responses. Therefore, we sought to determine what, if any DC subset(s) upregulate c-kit after in vivo treatment. A basal level of c-kit expression was found on CD11c-positive, low autofluorescent DCs expressing CD11b/CX3CR1, which was upregulated following intratracheal administration of OVA/CT. Surprisingly, OVA/CpG also upregulated c-kit on CD11b/CX3CR1 DCs in vivo to an extent even greater than OVA/CT. DC expression of c-kit was highest where MHC Class II expression was also highest (i.e. following OVA/CpG treatment) suggesting that it may be linked to the activation state. However, c-kit on DCs migrating to the lung-draining lymph nodes (LNs) was markedly higher on cells from OVA/CT- versus OVA/CpG-treated animals. LN resident DCs also expressed c-kit, but it was not different between naïve and treated animals. Importantly, c-kit does appear to have functional consequences since c-kit-deficient DCs induce less IL-17 production in particular from naïve T cells, possibly due to their own decreased production of IL-6. These data suggest that c-kit expression, and possibly interaction with its ligand, stem cell factor, is important for migration to draining LNs and for skewing naïve T cell priming by DCs.