Imperial College London

DrDaphneStapels

Faculty of MedicineDepartment of Medicine

Honorary Research Associate
 
 
 
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Contact

 

d.stapels

 
 
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Location

 

Flowers buildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Boross:2014:10.4049/jimmunol.1302012,
author = {Boross, P and van, Montfoort N and Stapels, DAC and van, der Poel CE and Bertens, C and Meeldijk, J and Jansen, JHM and Verbeek, JS and Ossendorp, F and Wubbolts, R and Leusen, JHW},
doi = {10.4049/jimmunol.1302012},
journal = {J Immunol},
pages = {5506--5514},
title = {FcRγ-chain ITAM signaling is critically required for cross-presentation of soluble antibody-antigen complexes by dendritic cells.},
url = {http://dx.doi.org/10.4049/jimmunol.1302012},
volume = {193},
year = {2014}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - The uptake of Ag-Ab immune complexes (IC) after the ligation of activating FcγR on dendritic cells (DC) leads to 100 times more efficient Ag presentation than the uptake of free Ags. FcγRs were reported to facilitate IC uptake and simultaneously induce cellular activation that drives DC maturation and mediates efficient T cell activation. Activating FcγRs elicit intracellular signaling via the ITAM domain of the associated FcRγ-chain. Studies with FcRγ-chain knockout (FcRγ(-/-)) mice reported FcRγ-chain ITAM signaling to be responsible for enhancing both IC uptake and DC maturation. However, FcRγ-chain is also required for surface expression of activating FcγRs, hampering the dissection of ITAM-dependent and independent FcγR functions in FcRγ(-/-) DCs. In this work, we studied the role of FcRγ-chain ITAM signaling using DCs from NOTAM mice that express normal surface levels of activating FcγR, but lack functional ITAM signaling. IC uptake by bone marrow-derived NOTAM DCs was reduced compared with wild-type DCs, but was not completely absent as in FcRγ(-/-) DCs. In NOTAM DCs, despite the uptake of ICs, both MHC class I and MHC class II Ag presentation was completely abrogated similar to FcRγ(-/-) DCs. Secretion of cytokines, upregulation of costimulatory molecules, and Ag degradation were abrogated in NOTAM DCs in response to FcγR ligation. Cross-presentation using splenic NOTAM DCs and prolonged incubation with OVA-IC was also abrogated. Interestingly, in this setup, proliferation of CD4(+) OT-II cells was induced by NOTAM DCs. We conclude that FcRγ-chain ITAM signaling facilitates IC uptake and is essentially required for cross-presentation, but not for MHC class II Ag presentation.
AU - Boross,P
AU - van,Montfoort N
AU - Stapels,DAC
AU - van,der Poel CE
AU - Bertens,C
AU - Meeldijk,J
AU - Jansen,JHM
AU - Verbeek,JS
AU - Ossendorp,F
AU - Wubbolts,R
AU - Leusen,JHW
DO - 10.4049/jimmunol.1302012
EP - 5514
PY - 2014///
SP - 5506
TI - FcRγ-chain ITAM signaling is critically required for cross-presentation of soluble antibody-antigen complexes by dendritic cells.
T2 - J Immunol
UR - http://dx.doi.org/10.4049/jimmunol.1302012
UR - https://www.ncbi.nlm.nih.gov/pubmed/25355925
VL - 193
ER -