| First Author | Shimanaka Y | Year | 2017 |
| Journal | Nat Med | Volume | 23 |
| Issue | 11 | Pages | 1287-1297 |
| PubMed ID | 29035365 | Mgi Jnum | J:254385 |
| Mgi Id | MGI:6102964 | Doi | 10.1038/nm.4417 |
| Citation | Shimanaka Y, et al. (2017) Omega-3 fatty acid epoxides are autocrine mediators that control the magnitude of IgE-mediated mast cell activation. Nat Med 23(11):1287-1297 |
| abstractText | Critical to the function of mast cells in immune responses including allergy is their production of lipid mediators, among which only omega-6 (omega-6) arachidonate-derived eicosanoids have been well characterized. Here, by employing comprehensive lipidomics, we identify omega-3 (omega-3) fatty acid epoxides as new mast cell-derived lipid mediators and show that they are produced by PAF-AH2, an oxidized-phospholipid-selective phospholipase A2. Genetic or pharmacological deletion of PAF-AH2 reduced the steady-state production of omega-3 epoxides, leading to attenuated mast cell activation and anaphylaxis following FcvarepsilonRI cross-linking. Mechanistically, the omega-3 epoxides promote IgE-mediated activation of mast cells by downregulating Srcin1, a Src-inhibitory protein that counteracts FcvarepsilonRI signaling, through a pathway involving PPARg. Thus, the PAF-AH2-omega-3 epoxide-Srcin1 axis presents new potential drug targets for allergic diseases. |
