| Autor: |
Li, Qian, Li, Dulei, Zhang, Xian, Wan, Qingqing, Zhang, Wen, Zheng, Mingke, Zou, Le, Elly, Chris, Lee, Jee H., Liu, Yun-Cai |
| Jazyk: |
angličtina |
| Rok vydání: |
2018 |
| Předmět: |
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| Popis: |
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 1α (HIF1α) and attenuated interleukin-33 (IL-33) receptor ST2 expression, which was rectified by HIF1α ablation or inhibition. HIF1α-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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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