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

• Published in: Nature medicine Vol. 20; no. 12; pp. 1458 - 1463
• Main Authors: Clatworthy, Menna R, Aronin, Caren E Petrie, Mathews, Rebeccah J, Morgan, Nicole Y, Smith, Kenneth G C, Germain, Ronald N
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.12.2014; Nature Publishing Group
• Subjects: 14; 14/19; 14/69; 631/250/2503; 631/250/38; Animals; Antigen-Antibody Complex - immunology; Antigens; Autoimmune diseases; Biomedicine; Cancer Research; Cell adhesion & migration; Cell migration; Cell Movement - immunology; Chemokine CCL19 - immunology; Chemokine receptors; Dendritic cells; Dendritic Cells - immunology; Genetic aspects; Humans; Immune response; Infectious Diseases; Langerhans Cells - immunology; letter; Lupus Erythematosus, Systemic - immunology; Lymph nodes; Lymph Nodes - immunology; Lymphatic system; Metabolic Diseases; Mice; Microscopy; Molecular Medicine; Neurosciences; Physiological aspects; Receptors, CCR7 - immunology; Receptors, IgG - immunology; T cell receptors; United Kingdom
• ISSN: 1078-8956; 1546-170X
• DOI: 10.1038/nm.3709

Immune complexes from mouse models of systemic lupus erythematosus and from humans with the disease promote dendritic cell migration in vivo . 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 1 , 2 . 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.