PMID- 25384086 OWN - NLM STAT- MEDLINE DCOM- 20150210 LR - 20181113 IS - 1546-170X (Electronic) IS - 1078-8956 (Print) IS - 1078-8956 (Linking) VI - 20 IP - 12 DP - 2014 Dec TI - Immune complexes stimulate CCR7-dependent dendritic cell migration to lymph nodes. PG - 1458-63 LID - 10.1038/nm.3709 [doi] AB - 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 Fcgamma receptors (FcgammaRs), 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 FcgammaR 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 FcgammaRIIB. 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. FAU - Clatworthy, Menna R AU - Clatworthy MR AD - 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. FAU - Aronin, Caren E Petrie AU - Aronin CE AD - Laboratory of Systems Biology, Lymphocyte Biology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. FAU - Mathews, Rebeccah J AU - Mathews RJ AD - Department of Medicine, MRC Laboratory of Molecular Biology, University of Cambridge, Cambridge, UK. FAU - Morgan, Nicole Y AU - Morgan NY AD - Biomedical Engineering and Physical Sciences Resource, Microfabrication and Microfluidics Unit, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland, USA. FAU - Smith, Kenneth G C AU - Smith KG AD - Cambridge Institute for Medical Research and Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, UK. FAU - Germain, Ronald N AU - Germain RN AD - Laboratory of Systems Biology, Lymphocyte Biology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. LA - eng GR - 081020/Wellcome Trust/United Kingdom GR - 100140/Wellcome Trust/United Kingdom GR - Intramural NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Intramural PT - Research Support, Non-U.S. Gov't DEP - 20141110 PL - United States TA - Nat Med JT - Nature medicine JID - 9502015 RN - 0 (Antigen-Antibody Complex) RN - 0 (Chemokine CCL19) RN - 0 (Fc gamma receptor IIB) RN - 0 (Receptors, CCR7) RN - 0 (Receptors, IgG) SB - IM MH - Animals MH - Antigen-Antibody Complex/*immunology MH - Cell Movement/*immunology MH - Chemokine CCL19/immunology MH - Dendritic Cells/immunology MH - Humans MH - Langerhans Cells/*immunology MH - Lupus Erythematosus, Systemic/*immunology MH - Lymph Nodes/*immunology MH - Mice MH - Receptors, CCR7/*immunology MH - Receptors, IgG/*immunology PMC - PMC4283039 MID - EMS60150 OID - NLM: EMS60150 EDAT- 2014/11/11 06:00 MHDA- 2015/02/11 06:00 PMCR- 2015/06/01 CRDT- 2014/11/11 06:00 PHST- 2014/07/13 00:00 [received] PHST- 2014/08/25 00:00 [accepted] PHST- 2014/11/11 06:00 [entrez] PHST- 2014/11/11 06:00 [pubmed] PHST- 2015/02/11 06:00 [medline] PHST- 2015/06/01 00:00 [pmc-release] AID - nm.3709 [pii] AID - 10.1038/nm.3709 [doi] PST - ppublish SO - Nat Med. 2014 Dec;20(12):1458-63. doi: 10.1038/nm.3709. Epub 2014 Nov 10.