Angiotensin AT2 receptor-induced interleukin-10 attenuates neuromyelitis optica spectrum disorder-like pathology

Research output: Contribution to journalJournal articleResearchpeer-review

  • Reza Khorooshi
  • Emil Ulrikkaholm Tofte-Hansen
  • Camilla Tygesen
  • Montañana-Rosell, Roser
  • Hannah Liska Limburg
  • Joanna Marczynska
  • Nasrin Asgari
  • Ulrike Muscha Steckelings
  • Trevor Owens

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing inflammatory central nervous system (CNS) disease for which there is no cure. Immunoglobulin G autoantibodies specific for the water channel aquaporin-4 are a serum biomarker, believed to induce complement-dependent astrocyte damage with secondary demyelination.

OBJECTIVE: To investigate the effect of angiotensin AT2 receptor (AT2R) stimulation on NMOSD-like pathology and its underlying mechanism.

METHODS: NMOSD-like pathology was induced in mice by intracerebral injection of immunoglobulin-G isolated from NMOSD patient serum, with complement. This mouse model produces the characteristic histological features of NMOSD. A specific AT2R agonist, Compound 21 (C21), was given intracerebrally at day 0 and by intrathecal injection at day 2.

RESULTS: Loss of aquaporin-4 and glial fibrillary acidic protein was attenuated by treatment with C21. Administration of C21 induced mRNA for interleukin-10 in the brain. NMOSD-like pathology was exacerbated in interleukin-10-deficient mice, suggesting a protective role. C21 treatment did not attenuate NMOSD-like pathology in interleukin-10-deficient mice, indicating that the protective effect of AT2R stimulation was dependent on interleukin-10.

CONCLUSION: Our findings identify AT2R as a novel potential therapeutic target for the treatment of NMOSD. Interleukin-10 signaling is an essential part of the protective mechanism counteracting NMOSD pathology.

Original languageEnglish
JournalMultiple Sclerosis Journal
Number of pages10
Publication statusPublished - 1 Sep 2020
Externally publishedYes

ID: 247995753