C-type lectin receptors (CLR) play an important role in
the immune system by recognising molecular patterns expressed by exogenous and
endogenous threats. Due to their ability to internalise antigens and modulate
signals from other receptors, CLR are attractive target for therapeutic immune
manipulation. CD302 is a newly discovered CLR that was previously shown to be
expressed by human myeloid phagocytes including macrophage (Mph), monocytes,
granulocytes and dendritic cells (DC). This molecule was hypothesised to play a
role in cell adhesion or migration due to its colocalisation with the f-actin
cytoskeleton in human monocyte derived Mph and CD302 transfected COS-1 cells. Our
study aims to clarify the immunological function of CD302 using mouse models. We
first characterised the transcriptional expression of CD302 in the mouse immune
cells using real-time PCR. CD302 was expressed by mouse Mph, granulocytes and
DC as in human. A more detailed analysis on DC revealed the novel observation that
CD302 was highly expressed by all migratory populations in lymph nodes (LN)
compared to resident subsets. A CD302 knock-out (KO) mouse strain was generated
lacking exon 1 of the gene, abrogating Cd302
transcription. Investigation of immune cell populations in various lymphoid
organs by flow cytometry uncovered a deficiency in migratory DC number and
proportion within LN of the CD302KO mice, compared to wild type (WT) mice. In vitro studies showed CD302KO DC had an
equivalent capacity to be activated by various stimuli, prime T cells and
migrate towards the lymphoid homing chemokines CCL19 and CCL21 compared to WT
DC. In contrast, CD302KO migratory DC had impaired migration from peripheral skin
to draining LN in a FITC painting in vivo
migration assay. These data and our recent observation on the morphology of
WT and CD302KO GM-CSF cultured bone marrow DC suggested that CD302 plays an
essential role in cell migration for an effective immune response.