| First Author | Cui S | Year | 2020 |
| Journal | Sci Adv | Volume | 6 |
| Issue | 43 | PubMed ID | 33087357 |
| Mgi Jnum | J:347953 | Mgi Id | MGI:6798975 |
| Doi | 10.1126/sciadv.aaz7290 | Citation | Cui S, et al. (2020) CD1d1 intrinsic signaling in macrophages controls NLRP3 inflammasome expression during inflammation. Sci Adv 6(43) |
| abstractText | Dysregulation of immune responses in the gut often associates with inflammatory bowel diseases (IBD). Mouse CD1d1, an ortholog of human CD1d mainly participating in lipid-antigen presentation to NKT cells, is able to generate intrinsic signals upon stimulation. Mice with macrophage-specific CD1d1 deficiency (Lym(CD1d1-/-) ) acquire resistance to dextran sodium sulfate (DSS)-induced colitis, attributing to the transcriptional inhibition of NLRP3 inflammasome components. The hyperactivation of NLRP3 inflammasome accounts for gut epithelial proliferation and intestine-blood barrier integrity. Mechanistically, occupancy by the natural ligand glycosphingolipid iGb3, CD1d1 responds with intracellular Ser(330) dephosphorylation thus to reduce the Peroxiredoxin 1 (PRDX1)-associated AKT-STAT1 phosphorylation and subsequent NF-kappaB activation, eventually causing transcriptional down-regulation of Nlrp3 and its immediate substrates Il1b and Il18 in macrophages. Therefore, the counterbalancing role of CD1d1 in macrophages appears to determine severity of DSS-mediated colitis in mice. These findings propose new intervention strategies for treating IBD and other inflammatory disorders. |
