AAV9-mediated AIRE gene delivery clears circulating antibodies and tissue T-cell infiltration in a mouse model of autoimmune polyglandular syndrome type-1.

ABSTRACT:

Objectives

Autoimmune polyglandular syndrome type-1 (APS-1) is a monogenic recessive disorder characterised by multiple endocrine abnormalities, chronic mucocutaneous candidiasis and high titres of serum autoantibodies. To date, no curative treatment is available; current therapies manage the symptoms rather than treating the cause and have major side effects. APS-1 is caused by mutations in the autoimmune regulator (AIRE) gene. AIRE mediates central tolerance by directing the ectopic expression of tissue-specific antigens (TSAs) in medullary thymic epithelial cells, causing the deletion of self-reactive thymocytes. Therefore, loss-of-function mutations in AIRE result in a multisystem autoimmune disease. Because of the monogenic aetiology of APS-1 and availability of

SUBMITTER: Almaghrabi S 

PROVIDER: S-EPMC7507015 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature