| First Author | Gupta AS | Year | 2019 |
| Journal | Glia | Volume | 67 |
| Issue | 8 | Pages | 1449-1461 |
| PubMed ID | 30957303 | Mgi Jnum | J:277920 |
| Mgi Id | MGI:6315065 | Doi | 10.1002/glia.23619 |
| Citation | Gupta AS, et al. (2019) RelB controls adaptive responses of astrocytes during sterile inflammation. Glia 67(8):1449-1461 |
| abstractText | In response to brain injury or infections, astrocytes become reactive, undergo striking morphological and functional changes, and secrete and respond to a spectrum of inflammatory mediators. We asked whether reactive astrocytes also display adaptive responses during sterile IL-1beta-induced neuroinflammation, which may limit tissue injury associated with many disorders of the central nervous system. We found that astrocytes display days-to-weeks long specific tolerance of cytokine genes, which is coordinated by NF-kappaB family member, RelB. However, in contrast to innate immune cells, astrocytic tolerance does not involve epigenetic silencing of the cytokine genes. Establishment of tolerance depends on persistent higher levels of RelB in tolerant astrocytes and its phosphorylation on serine 472. Mechanistically, this phosphorylation prevents efficient removal of RelB from cytokine promoters by IkappaBalpha and helps to establish tolerance. Importantly, ablation of RelB from astrocytes in mice abolishes tolerance during experimental neuroinflammation in vivo. |
