Abstract

How certain autoimmune diseases target specific organs remains obscure. In the 'K/BxN' arthritis model, autoantibodies to a ubiquitous antigen elicit joint-restricted pathology. Here we have used intravital imaging to demonstrate that transfer of arthritogenic antibodies caused macromolecular vasopermeability localized to sites destined to develop arthritis, augmenting its severity. Vasopermeability depended on mast cells, neutrophils and FcgammaRIII but not complement, tumor necrosis factor or interleukin 1. Unexpectedly, radioresistant FcRgamma-expressing cells in an organ distant from the joint were required. Histamine and serotonin were critical, and systemic administration of these vasoactive amines recapitulated the joint localization of immune complex-triggered vasopermeability. We propose that regionally distinct vascular properties 'interface' with immune effector pathways to foster organ-specific autoimmune damage, perhaps explaining why arthritis accompanies many human infectious and autoimmune disorders.