Mastering Immunity Europe 2017
Dr. Menna Clatworthy, University Lecturer in Transplantation Medicine, University of Cambridge, UK
Immune complexes modulate immune highways and DC trafficking
Antibodies are critical for defence against infection but may also be pathogenic in some autoimmune diseases. Many effector functions of antibody are mediated by Fcγ receptors (FcγRs), which are found on most immune cells, including dendritic cells (DCs). We demonstrate that FcγR engagement by IgG immune complexes (IC) stimulates DC migration from peripheral tissues to the paracortex of draining lymph nodes. Using intravital two-photon microscopy, we observed that local administration of model IC or autoantibody-containing IC from patients with systemic lupus erythematosus (SLE), resulted in dermal DC mobilisation. We confirmed that dermal DC migration to lymph nodes was CCR7-dependent and increased in the absence of the inhibitory receptor, FcγRIIb. Together, these data suggest an additional mechanism by which ICs might drive autoimmunity in SLE via the inappropriate localisation of autoantigen-bearing DC and may also have implications for boost strategies in vaccination.
Menna Clatworthy read Medicine at Cardiff, completed her professional training in nephrology at Cambridge and undertook a PhD at the University of Cambridge, investigating the role of IgG and FcγRs in autoimmunity and infection. She was awarded the British Renal Association Raine Award and the Academy of Medical Sciences/Medical Research Society Young Investigator Award for this work. She subsequently completed a Wellcome Trust Intermediate Fellowship at Cambridge and the National Institutes of Health, Bethesda, USA.
