Fig. 2.

Type 1 Interferon signalling and production [18••]. The innate immune system has developed sensing mechanisms against nucleic acid components as a defence against viral infections. Sensing of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) is controlled by separate signalling pathways with the common final result of increased production of type 1 interferon (IFN). An autocrine feedback loop occurs via the IFN-α receptor (IFNAR), further contributing to upregulation of IFN secretion. Mutations in genes regulating key sensing mechanisms, such as TREX1, SAMHD1 and STING, can produce aberrantly high type 1 IFN levels, a defining characteristic of interferonopathies. cGAMP: cyclic GMP-AMP; cGAS: cyclic GMP-AMP synthase; IRF: interferon-regulatory factor; JAK: janus kinase; IFN: interferon; MAVS: mitochondrial anti-viral signalling; MDA5: melanoma differentiation-associated protein 5; RIG-I: retinoic acid-inducible-I; STING: stimulator of interferon genes