| First Author | Wang X | Year | 2019 |
| Journal | EMBO J | Volume | 38 |
| Issue | 10 | PubMed ID | 30944096 |
| Mgi Jnum | J:277215 | Mgi Id | MGI:6323108 |
| Doi | 10.15252/embj.2018100947 | Citation | Wang X, et al. (2019) OTUB1 inhibits CNS autoimmunity by preventing IFN-gamma-induced hyperactivation of astrocytes. EMBO J 38(10) |
| abstractText | Astrocytes are critical regulators of neuroinflammation in multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). Growing evidence indicates that ubiquitination of signaling molecules is an important cell-intrinsic mechanism governing astrocyte function during MS and EAE Here, we identified an upregulation of the deubiquitinase OTU domain, ubiquitin aldehyde binding 1 (OTUB1) in astrocytes during MS and EAE Mice with astrocyte-specific OTUB1 ablation developed more severe EAE due to increased leukocyte accumulation, proinflammatory gene transcription, and demyelination in the spinal cord as compared to control mice. OTUB1-deficient astrocytes were hyperactivated in response to IFN-gamma, a fingerprint cytokine of encephalitogenic T cells, and produced more proinflammatory cytokines and chemokines than control astrocytes. Mechanistically, OTUB1 inhibited IFN-gamma-induced Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling by K48 deubiquitination and stabilization of the JAK2 inhibitor suppressor of cytokine signaling 1 (SOCS1). Thus, astrocyte-specific OTUB1 is a critical inhibitor of neuroinflammation in CNS autoimmunity. |
