CLEC10A Is a Specific Marker for Human CD1c+ Dendritic Cells and Enhances Their Toll-Like Receptor 7/8-Induced Cytokine Secretion

Abstract

Dendritic cells (DCs) are major players for the induction of immune responses. Apart from plasmacytoid DCs (pDCs), human DCs can be categorized into two types of conventional DCs: CD141+ DCs (cDC1) and CD1c+ DCs (cDC2). Defining uniquely expressed surface markers on human immune cells is not only important for the identification of DC subpopulations but also a prerequisite for harnessing the DC subset-specific potential in immunomodulatory approaches, such as antibody-mediated antigen targeting. Although others identified CLEC9A as a specific endocytic receptor for CD141+ DCs, such a receptor for CD1c+ DCs has not been discovered, yet. By performing transcriptomic and flow cytometric analyses on human DC subpopulations from different lymphohematopoietic tissues, we identified CLEC10A (CD301, macrophage galactose-type C-type lectin) as a specific marker for human CD1c+ DCs. We further demonstrate that CLEC10A rapidly internalizes into human CD1c+ DCs upon binding of a monoclonal antibody directed against CLEC10A. The binding of a CLEC10A-specific bivalent ligand (the MUC-1 peptide glycosylated with N-acetylgalactosamine) is limited to CD1c+ DCs and enhances the cytokine secretion (namely TNFα, IL-8, and IL-10) induced by TLR 7/8 stimulation. Thus, CLEC10A represents not only a candidate to better define CD1c+ DCs—due to its high endocytic potential—CLEC10A also exhibits an interesting candidate receptor for future antigen-targeting approaches.

Increased cardiovascular and atherosclerosis markers in blood of older patients with atopic dermatitis

“…1). These increases in the older than 60-year age group, compared with younger patients with AD and their respective controls, included markers of cardiovascular risk (myoglobin/MB, GDF15, myeloperoxidase/MPO, ST2), atherosclerosis (CCL4, SORT1), dendritic cells (CD40, CLEC10A 21 regulation (CD274, HMOX1), cell adhesion (CDH3, CDH6), and apoptosis (FAS, TNFRSF21; P < .05) (Figs. 1 and 2B).…”

The C‐type lectin receptor MGL sensesN‐acetylgalactosamine on the uniqueStaphylococcus aureusST395 wall teichoic acid

“…MGL is expressed on a range of immune cells including human DCs and macrophages residing in skin and lymph nodes, blood CD1c + DCs, and immature moDCs (van Vliet, Gringhuis, Geijtenbeek, & van Kooyk, , Schutz & Hackstein, , Heger et al, ). To investigate the interaction of MGL with S .…”

“…These contrasting outcomes suggest that the context in which MGL is engaged influences how MGL affects DC responses. Indeed, previous reports have indicated that MGL triggering alone does not induce high cytokine secretion by CD1c + DCs but requires costimulation with Toll‐like receptor ligands to differentially affect IL‐8, IL‐10, and TNFα production (Heger et al, ; van Vliet et al, ). Because Toll‐like receptor ligands differ between Gram‐positive and Gram‐negative bacteria, this may explain the different effects on DC cytokine production that we observe here.…”

Resolving single-cell heterogeneity from hundreds of thousands of cells through sequential hybrid clustering and NMF

“…For example, each DC cell cluster was found to expresses unique marker genes with established roles in functionally distinct DC subsets (plasmacytoid, maturing CD1c+, CD1c+ and CD8+) ( Fig. 3f-i) 27,28,29,30,31 . It is important to note that all approaches tested failed to sufficiently define all of the discrete CD34+ progenitor cell populations in the entire HCA dataset that were clearly resolved from the independent analysis of these cells, suggesting that these methods are far from perfect.…”