PMID- 29755453 OWN - NLM STAT- MEDLINE DCOM- 20190613 LR - 20190613 IS - 1664-3224 (Print) IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 9 DP - 2018 TI - CLEC10A Is a Specific Marker for Human CD1c(+) Dendritic Cells and Enhances Their Toll-Like Receptor 7/8-Induced Cytokine Secretion. PG - 744 LID - 10.3389/fimmu.2018.00744 [doi] LID - 744 AB - 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 TNFalpha, 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. FAU - Heger, Lukas AU - Heger L AD - Department of Dermatology, Laboratory of Dendritic Cell Biology, Friedrich-Alexander Universitat Erlangen-Nurnberg (FAU), University Hospital Erlangen, Erlangen, Germany. FAU - Balk, Silke AU - Balk S AD - Department of Dermatology, Laboratory of Dendritic Cell Biology, Friedrich-Alexander Universitat Erlangen-Nurnberg (FAU), University Hospital Erlangen, Erlangen, Germany. FAU - Luhr, Jennifer J AU - Luhr JJ AD - Department of Dermatology, Laboratory of Dendritic Cell Biology, Friedrich-Alexander Universitat Erlangen-Nurnberg (FAU), University Hospital Erlangen, Erlangen, Germany. FAU - Heidkamp, Gordon F AU - Heidkamp GF AD - Department of Dermatology, Laboratory of Dendritic Cell Biology, Friedrich-Alexander Universitat Erlangen-Nurnberg (FAU), University Hospital Erlangen, Erlangen, Germany. FAU - Lehmann, Christian H K AU - Lehmann CHK AD - Department of Dermatology, Laboratory of Dendritic Cell Biology, Friedrich-Alexander Universitat Erlangen-Nurnberg (FAU), University Hospital Erlangen, Erlangen, Germany. FAU - Hatscher, Lukas AU - Hatscher L AD - Department of Dermatology, Laboratory of Dendritic Cell Biology, Friedrich-Alexander Universitat Erlangen-Nurnberg (FAU), University Hospital Erlangen, Erlangen, Germany. FAU - Purbojo, Ariawan AU - Purbojo A AD - Department of Pediatric Cardiac Surgery, Friedrich-Alexander Universitat Erlangen-Nurnberg (FAU), University Hospital Erlangen, Erlangen, Germany. FAU - Hartmann, Arndt AU - Hartmann A AD - Department of Pathology, Friedrich-Alexander Universitat Erlangen-Nurnberg (FAU), University Hospital Erlangen, Erlangen, Germany. FAU - Garcia-Martin, Fayna AU - Garcia-Martin F AD - Graduate School of Life Science and Faculty of Advanced Life Science, Hokkaido University, Sapporo, Japan. FAU - Nishimura, Shin-Ichiro AU - Nishimura SI AD - Graduate School of Life Science and Faculty of Advanced Life Science, Hokkaido University, Sapporo, Japan. FAU - Cesnjevar, Robert AU - Cesnjevar R AD - Department of Pediatric Cardiac Surgery, Friedrich-Alexander Universitat Erlangen-Nurnberg (FAU), University Hospital Erlangen, Erlangen, Germany. FAU - Nimmerjahn, Falk AU - Nimmerjahn F AD - Department of Biology, Chair of Genetics, Friedrich-Alexander Universitat Erlangen-Nurnberg (FAU), Erlangen, Germany. FAU - Dudziak, Diana AU - Dudziak D AD - Department of Dermatology, Laboratory of Dendritic Cell Biology, Friedrich-Alexander Universitat Erlangen-Nurnberg (FAU), University Hospital Erlangen, Erlangen, Germany. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180427 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Antigens, CD1) RN - 0 (CD1C protein, human) RN - 0 (CLEC10A protein, human) RN - 0 (Cytokines) RN - 0 (Glycoproteins) RN - 0 (Lectins, C-Type) RN - 0 (MUC1 protein, human) RN - 0 (Mucin-1) RN - 0 (TLR7 protein, human) RN - 0 (TLR8 protein, human) RN - 0 (Toll-Like Receptor 7) RN - 0 (Toll-Like Receptor 8) SB - IM MH - Adult MH - Antigens, CD1/*immunology MH - Cytokines/immunology MH - Dendritic Cells/*immunology MH - Glycoproteins/*immunology MH - Humans MH - Lectins, C-Type/*immunology MH - Mucin-1/immunology MH - Toll-Like Receptor 7/immunology MH - Toll-Like Receptor 8/immunology PMC - PMC5934495 OTO - NOTNLM OT - CD1c+ dendritic cells OT - CLEC10A OT - antigen targeting OT - cDC2 OT - dendritic cell subpopulations OT - lineage marker EDAT- 2018/05/15 06:00 MHDA- 2018/05/15 06:01 PMCR- 2018/01/01 CRDT- 2018/05/15 06:00 PHST- 2018/01/06 00:00 [received] PHST- 2018/03/26 00:00 [accepted] PHST- 2018/05/15 06:00 [entrez] PHST- 2018/05/15 06:00 [pubmed] PHST- 2018/05/15 06:01 [medline] PHST- 2018/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2018.00744 [doi] PST - epublish SO - Front Immunol. 2018 Apr 27;9:744. doi: 10.3389/fimmu.2018.00744. eCollection 2018.