2026-08-29T13:36:34Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/89562024-09-27T20:47:36Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609
Repisalud
author
Schetters, Sjoerd T T
author
Kruijssen, Laura J W
author
Crommentuijn, Matheus H W
author
Kalay, Hakan
author
Ochando, Jordi
author
den Haan, Joke M M
author
Garcia-Vallejo, Juan J
author
van Kooyk, Yvette
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
2020-01-29T11:41:19Z
2020-01-29T11:41:19Z
2018
Front Immunol. 2018 May 7;9:990.
10.3389/fimmu.2018.00990
1664-3224
Frontiers in immunology
29867967
http://hdl.handle.net/20.500.12105/8956
The efficacy of vaccination studies aimed at targeting antigens to human DC-SIGN (hDC-SIGN) have been notoriously difficult to study in vivo, as eight dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN) homologs have been described in mice. CD209a/SIGNR5 has been coined as the mouse DC-SIGN (mDC-SIGN) ortholog, based on its expression and location in the genome. Nonetheless, which properties of hDC-SIGN are covered by mDC-SIGN is poorly investigated. One of the most important functions of DC-SIGN is the induction of adaptive immunity. As such, the aim of this study is to determine the capability of mDC-SIGN to induce adaptive immune responses. Here, we show that mDC-SIGN is expressed on GM-CSF cultured bone marrow-derived dendritic cells (BMDCs) and macrophages. However, mDC-SIGN is an internalizing receptor which, unlike hDC-SIGN, quickly resurfaces after internalization. Binding of OVA-coupled anti-mDC-SIGN antibody by BMDCs leads to quick internalization, processing, and presentation to antigen-specific CD8+ and CD4+ T cells, which can be boosted using the TLR4 ligand, monophosphoryl lipid A. In the homeostatic condition, mDC-SIGN is mostly expressed on myeloid cells in the skin and spleen. A subcutaneous injection of fluorescent anti-mDC-SIGN reveals specific targeting to mDC-SIGN+ skin dendritic cells (DCs) and monocyte-derived DCs in situ. A subcutaneous vaccination strategy containing OVA-coupled anti-mDC-SIGN antibody generated antigen-specific polyfunctional CD8+ T cell and CD4+ T cell responses and a strong isotype-switched OVA-specific antibody response in vivo. We conclude that mDC-SIGN shows partly overlapping similarities to hDC-SIGN and that targeting mDC-SIGN provides a valuable approach to investigate the immunological function of DC-SIGN in vivo.
eng
CD209a
SIGNR5
Antigen delivery
Dendritic cell
Dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin
Vaccination
Mouse DC-SIGN/CD209a as Target for Antigen Delivery and Adaptive Immunity
journal article
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MouseDCSIGNCD209aAs_2018.pdf
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MouseDCSIGNCD209aAs_2018.pdf.txt