Dendritic cell-associated lectin 2 (DCAL2) defines a distinct CD8α− dendritic cell subset

• Published in: Journal of leukocyte biology Vol. 91; no. 3; pp. 437 - 448
• Main Authors: Kasahara, Shinji, Clark, Edward A.
• Format: Journal Article
• Language: English
• Published: United States Society for Leukocyte Biology 01.03.2012
• Subjects: Animals; Antigen-Presenting Cells - immunology; Antigen-Presenting Cells - metabolism; CD8 Antigens - metabolism; Cells, Cultured; Cytokines - biosynthesis; Cytokines - metabolism; C‐type lectin; Dendritic Cells - classification; Dendritic Cells - immunology; Dendritic Cells - metabolism; IFN‐γ; IL‐4; Immunophenotyping; Lectins, C-Type - genetics; Lectins, C-Type - immunology; Lectins, C-Type - metabolism; Male; Mice; Mice, Inbred C57BL; NIH 3T3 Cells; Receptors, Mitogen - genetics; Receptors, Mitogen - immunology; Receptors, Mitogen - metabolism; Receptors, Signal Transduction, & Genes; RNA, Messenger - metabolism; Th1; Th1 Cells - immunology; Th1 Cells - metabolism; Th2; Th2 Cells - immunology; Th2 Cells - metabolism; Toll-Like Receptors - metabolism; Toll‐like receptors
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1189/jlb.0711384

Surface expression of DCAL2 and DCIR2 subdivides CD8α‐DCs into functionally distinct subsets, which respond differently to TLR agonists and promote distinct Th responses. 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.