Nature Immunology 7, 284 - 292 (2006)
Published online: 29 January 2006; Corrected online: 07 February 2006 | doi:10.1038/ni1306
Particularities of the vasculature can promote the organ specificity of autoimmune attackBryce A Binstadt1, 2, 3, Pratik R Patel4, 6, Herlen Alencar1, 4, Peter A Nigrovic1, 3, 5, David M Lee1, 5, Umar Mahmood1, 4, Ralph Weissleder1, 4, Diane Mathis1, 2, 5
& Christophe Benoist1, 2, 51
Harvard Medical School, Boston, Massachusetts 02115, USA. 2
Section on Immunology and Immunogenetics, Joslin Diabetes Center, Boston, Massachusetts 02215, USA. 3
Rheumatology Program, Children's Hospital Boston, Boston, Massachusetts 02115, USA. 4
Center for Molecular Imaging Research, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA. 5
Division of Rheumatology, Immunology and Allergy and Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. 6
Present address: Novartis Institutes for BioMedical Research, Cambridge, Massachusetts 02139, USA.
Correspondence should be addressed to Diane Mathis cbdm@joslin.harvard.edu or Christophe Benoist cbdm@joslin.harvard.edu 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 Fc RIII but not complement, tumor necrosis factor or interleukin 1. Unexpectedly, radioresistant FcR-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.* Note: In the version of this article initially published online, the end of the third sentence of the second subsection of Results is incorrect. The sentence should read "Intravenous administration of preaggregated normal mouse IgG elicited an increase in joint-localized vasopermeability very similar to that induced by the administration of arthritogenic serum (Fig. 2b and data not shown)." Also, the final acknowledgement is incorrect; it should read "... and by the National Institute of Diabetes and Digestive and Kidney Diseases–supported Diabetes and Endocrinology Research Center cores of the Joslin Diabetes Center." The errors have been corrected for the HTML and print versions of the article.
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