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Proc Natl Acad Sci U S A. 2014 Aug 5;111(31):11419-24. doi: 10.1073/pnas.1410854111. Epub 2014 Jul 21.

Denervation protects limbs from inflammatory arthritis via an impact on the microvasculature.

Author information

1
Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114; and.
2
Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115.
3
Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115 dm@hms.harvard.edu.

Abstract

Two-way communication between the mammalian nervous and immune systems is increasingly recognized and appreciated. An intriguing example of such crosstalk comes from clinical observations dating from the 1930s: Patients who suffer a stroke and then develop rheumatoid arthritis atypically present with arthritis on only one side, the one not afflicted with paralysis. Here we successfully modeled hemiplegia-induced protection from arthritis using the K/BxN serum-transfer system, focused on the effector phase of inflammatory arthritis. Experiments entailing pharmacological inhibitors, genetically deficient mouse strains, and global transcriptome analyses failed to associate the protective effect with a single nerve quality (i.e., with the sympathetic, parasympathetic, or sensory nerves). Instead, there was clear evidence that denervation had a long-term effect on the limb microvasculature: The rapid and joint-localized vascular leak that typically accompanies and promotes serum-transferred arthritis was compromised in denervated limbs. This defect was reflected in the transcriptome of endothelial cells, the expression of several genes impacting vascular leakage or transendothelial cell transmigration being altered in denervated limbs. These findings highlight a previously unappreciated pathway to dissect and eventually target in inflammatory arthritis.

KEYWORDS:

autoantibody; inflammation; nervous system; vascular system

PMID:
25049388
PMCID:
PMC4128122
DOI:
10.1073/pnas.1410854111
[Indexed for MEDLINE]
Free PMC Article

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