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

Heger L, Balk S, Lühr J, Heidkamp GF, Lehmann C, Hatscher L, Purbojo A, Hartmann A, Garcia-Martin F, Nishimura SI, Cesnjevar R, Nimmerjahn F, Dudziak D (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Frontiers in Immunology Frontiers Research Foundation / Frontiers Media

Book Volume: 9

DOI: 10.3389/fimmu.2018.00744

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.

Authors with CRIS profile

Lukas Heger Department of Dermatology Jennifer Lühr Department of Obstetrics and Gynaecology Gordon Frederik Heidkamp Department of Dermatology Christian Lehmann Department of Dermatology Ariawan Purbojo Department of Paediatric Cardiac Surgery Arndt Hartmann Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie Robert Cesnjevar Department of Paediatric Cardiac Surgery Falk Nimmerjahn Lehrstuhl für Genetik Diana Dudziak Professur für die Biologie Dendritischer Zellen

Additional Organisation(s)

Interdisziplinäres Zentrum für Klinische Forschung

Involved external institutions

Hokkaido University (Hokudai) / 北海道大学 JP Japan (JP)

How to cite

APA:

Heger, L., Balk, S., Lühr, J., Heidkamp, G.F., Lehmann, C., Hatscher, L.,... Dudziak, D. (2018). CLEC10A Is a Specific Marker for Human CD1c+ Dendritic Cells and Enhances Their Toll-Like Receptor 7/8-Induced Cytokine Secretion. Frontiers in Immunology, 9. https://dx.doi.org/10.3389/fimmu.2018.00744

MLA:

Heger, Lukas, et al. "CLEC10A Is a Specific Marker for Human CD1c+ Dendritic Cells and Enhances Their Toll-Like Receptor 7/8-Induced Cytokine Secretion." Frontiers in Immunology 9 (2018).

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