| First Author | Blumer T | Year | 2017 |
| Journal | J Biol Chem | Volume | 292 |
| Issue | 43 | Pages | 17928-17938 |
| PubMed ID | 28900038 | Mgi Jnum | J:246805 |
| Mgi Id | MGI:5920109 | Doi | 10.1074/jbc.M117.788877 |
| Citation | Blumer T, et al. (2017) SOCS1 is an inducible negative regulator of interferon lambda (IFN-lambda)-induced gene expression in vivo. J Biol Chem 292(43):17928-17938 |
| abstractText | Type I (alpha and beta) and type III (lambda) IFNs are induced upon viral infection through host sensory pathways that activate IFN regulatory factors (IRFs) and nuclear factor kappaB. Secreted IFNs induce autocrine and paracrine signaling through the JAK-STAT pathway, leading to the transcriptional induction of hundreds of IFN-stimulated genes, among them sensory pathway components such as cGAS, STING, RIG-I, MDA5, and the transcription factor IRF7, which enhance the induction of IFN-alphas and IFN-lambdas. This positive feedback loop enables a very rapid and strong host response that, at some point, has to be controlled by negative regulators to maintain tissue homeostasis. Type I IFN signaling is controlled by the inducible negative regulators suppressor of cytokine signaling 1 (SOCS1), SOCS3, and ubiquitin-specific peptidase 18 (USP18). The physiological role of these proteins in IFN-gamma signaling has not been clarified. Here we used knockout cell lines and mice to show that IFN-lambda signaling is regulated by SOCS1 but not by SOCS3 or USP18. These differences were the basis for the distinct kinetic properties of type I and III IFNs. We found that IFN-alpha signaling is transient and becomes refractory after hours, whereas IFN-lambda provides a long-lasting IFN-stimulated gene induction. |
