Particularities of the vasculature can promote the organ specificity of autoimmune attack

Bryce A. Binstadt, Pratik R. Patel, Herlen Alencar, Peter A. Nigrovic, David M. Lee, Umar Mahmood, Ralph Weissleder, Diane Mathis, Christophe Benoist

Research output: Contribution to journalArticlepeer-review

145 Scopus citations

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 FcγRIII but not complement, tumor necrosis factor or interleukin 1. Unexpectedly, radioresistant FcRγ-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.

Original languageEnglish (US)
Pages (from-to)284-292
Number of pages9
JournalNature immunology
Volume7
Issue number3
DOIs
StatePublished - Mar 1 2006

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