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

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

Publikation: Bidrag til tidsskriftArtikelForskningpeer review

Abstrakt

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.

OriginalsprogEngelsk
Sider (fra-til)1187-1196
Antal sider10
TidsskriftMultiple Sclerosis Journal
Vol/bind26
Udgave nummer10
DOI
StatusUdgivet - sep. 2020

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