title: Temporal profile of magnetic resonance angiography and decreased ratio of regulatory T cells after immunological adjuvant administration to mice lacking RNF213, a susceptibility gene for moyamoya disease.
abstract: Moyamoya disease (MMD) is a chronic, occlusive cerebrovascular disease with an unknown etiology and is characterized by an abnormal vascular network at the base of the brain. Recent studies identified the RNF213 gene (RNF213) as an important susceptibility gene for MMD; however, the mechanisms underlying the RNF213 abnormality related to MMD have not yet been elucidated. We previously reported that Rnf213-deficient mice and Rnf213 p. R4828K knock-in mice did not spontaneously develop MMD, indicating the importance of secondary insults in addition to genetic factors in the pathogenesis of MMD. The most influential secondary insult is considered to be an immunological reaction because RNF213 is predominantly expressed in immunological tissues. Therefore, we herein attempted to evaluate the role of an immunological stimulation as a supplementary insult to the target disruption of RNF213 in the pathophysiology of MMD. Rnf213-deficient mice were treated with strong immunological adjuvants including muramyl dipeptide (MDP)-Lys (L18), and then underwent time-sequential magnetic resonance angiography (MRA) up to 40 weeks of age. The results obtained did not reveal any characteristic finding of MMD, and no significant difference was observed in MRA findings or the anatomy of the circle of Willis between Rnf213-deficient mice and wild-type mice after the administration of MDP-Lys (L18). The ratio of regulatory T cells after the administration of MDP-Lys (L18) was significantly decreased in Rnf213-deficient mice (p<0.01), suggesting the potential role of the RNF213 abnormality in the differentiation of regulatory T cells. Although the mechanisms underlying the development of MMD currently remain unclear, the RNF213 abnormality may compromise immunological self-tolerance, thereby contributing to the development of MMD.
authors.affiliation: Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kanoke
authors.affiliation: Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Japan. Electronic address: fujimur@nsg.med.tohoku.ac.jp.
authors.forename: Miki
authors.initials: M
authors.lastname: Fujimura
authors.affiliation: Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Kuniyasu
authors.initials: K
authors.lastname: Niizuma
authors.affiliation: Department of Dermatology, Tohoku University Graduate School of Medicine, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Fujimura
authors.affiliation: Department of Dermatology, Tohoku University Graduate School of Medicine, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Kakizaki
authors.affiliation: Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Ito
authors.affiliation: Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sakata
authors.affiliation: Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Sato-Maeda
authors.affiliation: Department of Pediatrics, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Kure
authors.affiliation: Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Teiji
authors.initials: T
authors.lastname: Tominaga
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D002452:Cell Count; D002941:Circle of Willis / Q000276:immunology / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D018810:Magnetic Resonance Angiography; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009072:Moyamoya Disease / Q000235:genetics* / Q000276:immunology* / Q000473:pathology*; D017634:Self Tolerance; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D000276:Adjuvants, Immunologic; C583291:RNF213 protein, mouse; D044767:Ubiquitin-Protein Ligases; D000251:Adenosine Triphosphatases
keywords: Magnetic resonance angiography (MRA); Moyamoya disease; Muramyl dipeptide (MDP)-Lys (L18); RNF213; Regulatory T cells