Rheumatoid arthritis is an organ-specific autoimmune disease. Using the well-established K/BxN arthritis model, our group could show several years ago that particularities of the vasculature are responsible for this feature. That study highlighted the importance of vascular permeability in the development of arthritis by allowing immune complexes as well as immune effector cells to leave the circulation and enter the peri-articular space. Vasoactive amines, mast cells, neutophils and FcgRIII were identified as critical parts for development of early site-restricted permeability after injection of K/BxN arthritic serum.
Now, our group found further evidence for the key role that the vasculature, in particular endothelial cells play in the development of arthritis. Starting with the long-known clinical observation of hemiplegia-induced sparing of joints we were able to model the phenomenon in the K/BxN serum-transfer system by unilateral denervation. The result is a near-complete abrogation of clinically detectable arthritis in denervated joints. This observation adds to the increasing body of data that suggest a crosstalk between the immune and nervous system; the exact anatomic correlate that governs the interaction remains to be found. Interestingly, however, our data demonstrate that the rapid and joint-localized vascular leak that typically accompanies and promotes serum-transferred arthritis was compromised in those denervated limbs. Attempts at rescuing the leak with histamine or serotonin that were successful in our previous work failed in the current study. This prominent defect was reflected in the transcriptome of endothelial cells: the expression of several genes impacting vascular leakage or transendothelial cell transmigration were altered in denervated limbs. These findings highlight a previously unappreciated pathway to dissect and eventually target in inflammatory arthritis.
Disclosure of Interest None declared
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