MYSM1 Represses Innate Immunity and Autoimmunity through Suppressing the cGAS-STING Pathway.
Cell Rep
; 33(3): 108297, 2020 10 20.
Article
en En
| MEDLINE
| ID: mdl-33086059
ABSTRACT
The immune system is not only required for preventing threats exerted by pathogens but also essential for developing immune tolerance to avoid tissue damage. This study identifies a distinct mechanism by which MYSM1 suppresses innate immunity and autoimmunity. The expression of MYSM1 is induced upon DNA virus infection and by intracellular DNA stimulation. MYSM1 subsequently interacts with STING and cleaves STING K63-linked ubiquitination to suppress cGAS-STING signaling. Notably, Mysm1-deficient mice exhibit a hyper-inflammatory response, acute tissue damage, and high mortality upon virus infection. Moreover, in the PBMCs of patients with systemic lupus erythematosus (SLE), MYSM1 production decreases, while type I interferons and pro-inflammatory cytokine expressions increase. Importantly, MYSM1 treatment represses the production of IFNs and pro-inflammatory cytokines in the PBMCs of SLE patients. Thus, MYSM1 is a critical repressor of innate immunity and autoimmunity and is thus a potential therapeutic agent for infectious, inflammatory, and autoimmune diseases.
Palabras clave
ADV; HSV-1; MYSM1; Myb-like; SLE; STING; SWIRM; adenovirus; and MPN domains 1 protein; autoimmune disease; autoimmunity; cGAS; cyclic GMP-AMP synthase; herpes simplex virus type 1; innate immunity; pro-inflammatory cytokines; stimulator of interferon genes; systemic lupus erythematosus; type I interferon
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Transactivadores
/
Proteasas Ubiquitina-Específicas
/
Proteínas de la Membrana
/
Nucleotidiltransferasas
Tipo de estudio:
Prognostic_studies
Límite:
Adult
/
Animals
/
Female
/
Humans
/
Male
/
Middle aged
País/Región como asunto:
Asia
Idioma:
En
Revista:
Cell Rep
Año:
2020
Tipo del documento:
Article
País de afiliación:
China