| First Author | Li Q | Year | 2018 |
| Journal | Immunity | Volume | 48 |
| Issue | 2 | Pages | 258-270.e5 |
| PubMed ID | 29452935 | Mgi Jnum | J:272363 |
| Mgi Id | MGI:6284445 | Doi | 10.1016/j.immuni.2017.12.013 |
| Citation | Li Q, et al. (2018) E3 Ligase VHL Promotes Group 2 Innate Lymphoid Cell Maturation and Function via Glycolysis Inhibition and Induction of Interleukin-33 Receptor. Immunity 48(2):258-270.e5 |
| abstractText | Group 2 innate lymphoid cells (ILC2s) are a specialized subset of lymphoid effector cells that are critically involved in allergic responses; however, the mechanisms of their regulation remain unclear. We report that conditional deletion of the E3 ubiquitin ligase VHL in innate lymphoid progenitors minimally affected early-stage bone marrow ILC2s but caused a selective and intrinsic decrease in mature ILC2 numbers in peripheral non-lymphoid tissues, resulting in reduced type 2 immune responses. VHL deficiency caused the accumulation of hypoxia-inducible factor 1alpha (HIF1alpha) and attenuated interleukin-33 (IL-33) receptor ST2 expression, which was rectified by HIF1alpha ablation or inhibition. HIF1alpha-driven expression of the glycolytic enzyme pyruvate kinase M2 downmodulated ST2 expression via epigenetic modification and inhibited IL-33-induced ILC2 development. Our study indicates that the VHL-HIF-glycolysis axis is essential for the late-stage maturation and function of ILC2s via targeting IL-33-ST2 pathway. |
