title: Denervation protects limbs from inflammatory arthritis via an impact on the microvasculature.
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.
authors: Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114; and.
authors: Lars
authors: L
authors: Stangenberg
authors: Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115.
authors: Dalia
authors: D
authors: Burzyn
authors: Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115.
authors: Bryce A
authors: BA
authors: Binstadt
authors: Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114; and.
authors: Ralph
authors: R
authors: Weissleder
authors: Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114; and.
authors: Umar
authors: U
authors: Mahmood
authors: Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115 dm@hms.harvard.edu.
authors: Christophe
authors: C
authors: Benoist
authors: Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115 dm@hms.harvard.edu.
authors: Diane
authors: D
authors: Mathis
mesh_terms: D000818:Animals; D000842:Ankle / Q000098:blood supply / Q000473:pathology; D001169:Arthritis, Experimental / Q000150:complications* / Q000473:pathology / Q000517:prevention & control*; D003714:Denervation; D004195:Disease Models, Animal; D006614:Hindlimb / Q000098:blood supply* / Q000294:innervation* / Q000473:pathology; D007249:Inflammation / Q000150:complications* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055806:Microvessels / Q000473:pathology*; D010243:Paralysis / Q000150:complications / Q000473:pathology; D044967:Serum / Q000378:metabolism; D059467:Transcriptome / Q000235:genetics
keywords: autoantibody; inflammation; nervous system; vascular system