| First Author | Zhang M | Year | 2024 |
| Journal | Cell Death Dis | Volume | 15 |
| Issue | 7 | Pages | 491 |
| PubMed ID | 38982043 | Mgi Jnum | J:350975 |
| Mgi Id | MGI:7664762 | Doi | 10.1038/s41419-024-06887-0 |
| Citation | Zhang M, et al. (2024) IL-27 disturbs lipid metabolism and restrains mitochondrial activity to inhibit gammadelta T17 cell-mediated skin inflammation. Cell Death Dis 15(7):491 |
| abstractText | IL-17+ gammadelta T cells (gammadelta T17) are kick-starters of inflammation due to their strict immunosurveillance of xenobiotics or cellular damages and rapid response to pro-inflammatory stimulators. IL-27 is a well-recognized pleiotropic immune regulator with potent inhibitory effects on type 17 immune responses. However, its actions on gammadelta T17 mediated inflammation and the underlying mechanisms are less well understood. Here we find that IL-27 inhibits the production of IL-17 from gammadelta T cells. Mechanistically, IL-27 promotes lipolysis while inhibits lipogenesis, thus reduces the accumulation of lipids and subsequent membrane phospholipids, which leads to mitochondrial deactivation and ensuing reduction of IL-17. More importantly, Il27ra deficient gammadelta T cells are more pathogenic in an imiquimod-induced murine psoriasis model, while intracutaneous injection of rmIL-27 ameliorates psoriatic inflammation. In summary, this work uncovered the metabolic basis for the immune regulatory activity of IL-27 in restraining gammadelta T17 mediated inflammation, which provides novel insights into IL-27/IL-27Ra signaling, gammadelta T17 biology and the pathogenesis of psoriasis. |
