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, 2018 02 20.
Article
em En
| MEDLINE
| ID: mdl-29452935
ABSTRACT
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.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Linfócitos
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Receptores de Interleucina
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Ubiquitina-Proteína Ligases
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Proteína Supressora de Tumor Von Hippel-Lindau
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Glicólise
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article