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Nat Med. 2014 Dec;20(12):1458-63. doi: 10.1038/nm.3709. Epub 2014 Nov 10.

Immune complexes stimulate CCR7-dependent dendritic cell migration to lymph nodes.

Author information

1
1] Department of Medicine, MRC Laboratory of Molecular Biology, University of Cambridge, Cambridge, UK. [2] Laboratory of Systems Biology, Lymphocyte Biology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
2
Laboratory of Systems Biology, Lymphocyte Biology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
3
Department of Medicine, MRC Laboratory of Molecular Biology, University of Cambridge, Cambridge, UK.
4
Biomedical Engineering and Physical Sciences Resource, Microfabrication and Microfluidics Unit, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland, USA.
5
Cambridge Institute for Medical Research and Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, UK.

Abstract

Antibodies are critical for defense against a variety of microbes, but they may also be pathogenic in some autoimmune diseases. Many effector functions of antibodies are mediated by Fcγ receptors (FcγRs), which are found on most immune cells, including dendritic cells (DCs)-important antigen-presenting cells that play a central role in inducing antigen-specific tolerance or immunity. Following antigen acquisition in peripheral tissues, DCs migrate to draining lymph nodes via the lymphatics to present antigen to T cells. Here we demonstrate that FcγR engagement by IgG immune complexes (ICs) stimulates DC migration from peripheral tissues to the paracortex of draining lymph nodes. In vitro, IC-stimulated mouse and human DCs showed greater directional migration in a chemokine (C-C) ligand 19 (CCL19) gradient and increased chemokine (C-C) receptor 7 (CCR7) expression. Using intravital two-photon microscopy, we observed that local administration of IC resulted in dermal DC mobilization. We confirmed that dermal DC migration to lymph nodes depended on CCR7 and increased in the absence of the inhibitory receptor FcγRIIB. These observations have relevance to autoimmunity because autoantibody-containing serum from humans with systemic lupus erythematosus (SLE) and from a mouse model of SLE also increased dermal DC migration in vivo, suggesting that this process may occur in lupus, potentially driving the inappropriate localization of autoantigen-bearing DCs.

PMID:
25384086
PMCID:
PMC4283039
DOI:
10.1038/nm.3709
[Indexed for MEDLINE]
Free PMC Article

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