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Mouse DC-SIGN/CD209a as Target for Antigen Delivery and Adaptive Immunity
- Source :
- Frontiers in Immunology, Frontiers in Immunology, 9. Frontiers Media S.A., Repisalud, Instituto de Salud Carlos III (ISCIII), Frontiers in Immunology, Vol 9 (2018), Schetters, S T T, Kruijssen, L J W, Crommentuijn, M H W, Kalay, H, Ochando, J, den Haan, J M M, Garcia-Vallejo, J J & van Kooyk, Y 2018, ' Mouse DC-SIGN/CD209a as Target for Antigen Delivery and Adaptive Immunity ', Frontiers in Immunology, vol. 9, pp. 990 . https://doi.org/10.3389/fimmu.2018.00990, https://doi.org/10.3389/fimmu.2018.00990
- Publication Year :
- 2018
- Publisher :
- Frontiers Media S.A., 2018.
-
Abstract
- 339977 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. This work was supported by the European Research Council Advanced grant 339977 to YK, SS, LK, and MC. Sí
- Subjects :
- 0301 basic medicine
CD4-Positive T-Lymphocytes
Male
Antigen delivery
Adaptive Immunity
CD8-Positive T-Lymphocytes
Animals, Genetically Modified
Mice
Immunology and Allergy
Original Research
Antigen Presentation
Vaccination
Acquired immune system
3. Good health
Cell biology
dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin
DC-SIGN
CD209a
medicine.anatomical_structure
Female
Dendritic cell
lcsh:Immunologic diseases. Allergy
dendritic cell
Ovalbumin
T cell
Antigen presentation
Immunology
Receptors, Cell Surface
Biology
Antibodies
03 medical and health sciences
Immune system
Antigen
medicine
Animals
Humans
Lectins, C-Type
Macrophages
Granulocyte-Macrophage Colony-Stimulating Factor
antigen delivery
Dendritic Cells
Dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin
Mice, Inbred C57BL
030104 developmental biology
SIGNR5
biology.protein
lcsh:RC581-607
Cell Adhesion Molecules
CD8
Subjects
Details
- Language :
- English
- ISSN :
- 16643224
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Frontiers in Immunology
- Accession number :
- edsair.doi.dedup.....f6fe8730decbda86e5841fcbe889f055