Dendritic Cell-Associated Lectin 2 (DCAL2) Defines a Distinct CD8α− Dendritic Cell Subset

ABSTRACT CLRs on DCs play important roles in immunity and are expressed selectively on certain DC subsets. Murine DCAL2 (myeloid inhibitory C-type lectin/Clec12a) is a type-II CLR with an ITIM. Using a mouse DCAL2-specific mAb, we found that DCAL2 is expressed at relatively high levels on APCs and that DCAL2 expression can be used to divide CD8α– DCs into DCAL2+DCIR2– and DCAL2–DCIR2+ subpopulations. CD8α–DCAL2+ DC, CD8α–DCIR2+ DC, and CD8α+DCAL2+ DC subsets each express different levels of TLRs and respond to unique classes of TLR ligands by producing distinct sets of cytokines. Whereas CD8α–DCAL2+ DCs robustly produce cytokines, including IL-12, in response to CpG, CD8α–DCIR2+ DCs produce only TNF-α and IL-10 in modest amounts when stimulated with zymosan. However, CD8α–DCIR2+ DCs, unlike the other DC subsets, strongly up-regulate OX40L when stimulated with bacterial flagellin. As predicted from their cytokine expression, CD8α–DCAL2+ DCs efficiently induced Th1 responses in the presence of CpG in vitro and in vivo, whereas CD8α–DCIR2+ DCs induced Th2 cells in response to flagellin. Thus, CD8α–DCAL2+ DCs comprise a distinct CD8α– DC subset capable of supporting Th1 responses. DCAL2 is a useful marker to identify a Th1-inducing CD8α– DC population.