Using PET imaging to track STING-induced interferon signaling
| Autor: | Howard A. Young, Enitome E. Bafor |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Multidisciplinary
Innate immune system Kinase Pattern recognition receptor Insect Bites and Stings Biology Immunity Innate Cell biology Immune system TANK-binding kinase 1 Tyrosine kinase 2 Interferon Positron-Emission Tomography medicine Commentary Animals Humans Interferons IRF3 medicine.drug Signal Transduction |
| Zdroj: | Proc Natl Acad Sci U S A |
| ISSN: | 1091-6490 |
| Popis: | In the 19th century, Ilya Metchnikoff defined and broadened our initial understanding of phagocytosis and, in 1908, went on to show that a cellular component (i.e., DNA) stimulates immune responses (1). About a century later, Janeway conceptualized pattern recognition receptors (PRRs) and pathogen-associated molecular patterns (PAMPs) (2). Since then, we know that PAMP recognition by innate immune cells via PRRs activates the production of several cytokines, including interferons (IFNs), with the eventual recruitment of lymphocytes. Subsequent research discovered that innate immune recognition of double-stranded DNA (dsDNA) triggers autoimmune diseases (3). However, before the discovery of dsDNA sensors, an endoplasmic reticulum (ER) protein encoded by the TMEM173 gene, known as a stimulator of IFN genes (STING), was identified as a significant factor involving DNA recognition in innate immunity (4). Subsequently, scientists discovered that the direct cytosolic DNA sensor (cGAS) activates the expression of type 1 IFNs (5). Today, it is well known that activation of cGAS-cGAMP-STING signaling is triggered by cytosolic DNA and is necessary for antimicrobial and antitumor immune responses. In PNAS, Liang et al. (6) describe an innovative process for monitoring STING-induced IFN signaling. Induction of IFN signaling by STING occurs on detection of cytoplasmic DNA, which may be tumor- or microbial-derived. STING is activated when cGAS catalyzes the synthesis of cyclic dinucleotides (CDNs) including 2′3′-cGAMP (7). STING is translocated from the ER to the perinucleus, phosphorylated by TANK-binding kinase 1 (TBK1) and recruits IFN regulatory factor 3 (IRF3), which in turn is phosphorylated by TBK1, forms a dimer, and enters the nucleus. Phosphorylated IRF3 activates transcription of type 1 IFNs and other relevant cytokines (8) which bind to the heterodimeric IFN receptors (IFNAR1 and IFNAR2) and recruits Janus family kinase 1(Jak1) and tyrosine kinase 2 (Tyk2), which in turn phosphorylates and activates IFNAR1 and IFNAR2. … [↵][1]1To whom correspondence may be addressed. Email: Enitome.Bafor{at}nih.gov or younghow{at}mail.nih.gov. [1]: #xref-corresp-1-1 |
| Databáze: | OpenAIRE |
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