STING-associated vasculopathy develops independently of IRF3 in mice.

ABSTRACT: Patients with stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI) develop systemic inflammation characterized by vasculopathy, interstitial lung disease, ulcerative skin lesions, and premature death. Autosomal dominant mutations in STING are thought to trigger activation of IRF3 and subsequent up-regulation of interferon (IFN)-stimulated genes (ISGs) in patients with SAVI. We generated heterozygous STING N153S knock-in mice as a model of SAVI. These mice spontaneously developed inflammation within the lung, hypercytokinemia, T cell cytopenia, skin ulcerations, and premature death. Cytometry by time-of-flight (CyTOF) analysis revealed that the STING N153S mutation caused myeloid cell expansion, T cell cytopenia, and dysregulation of immune cell signal

SUBMITTER: Warner JD 

PROVIDER: S-EPMC5679177 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature