ArticleE3LigaseVHLPromotesGroup2InnateLymphoidCellMaturationandFunctionviaGlycolysisInhibitionandInductionofInterleukin-33ReceptorGraphicalAbstractHighlightsdVHLpromotesmaturationofILC2sandlunginflammationdVHLintrinsicallyregulatesILC2developmentdTheVHL-HIFaxispromotestheexpressionoftheIL-33receptorST2dThePKM2-pyruvatecheckpointinhibitsepigeneticmodificationoftheST2geneAuthorsQianLi,DuleiLi,XianZhang,...,ChrisElly,JeeH.Lee,Yun-CaiLiuCorrespondenceyuncai_liu@mail.tsinghua.edu.cnInBriefILC2sarecriticallyinvolvedinallergicresponses,butthemechanismsbywhichtheyareregulatedremainunclear.Lietal.demonstratethattheVHL-HIFaxisisessentialforILC2maturationandfunctionviainhibitionofglycolysisandinductionofIL-33receptorexpression.Thesefindingshaveimplicationsforidentifyingtherapeutictargetsforallergicdiseases.Lietal.,2018,Immunity48,258–270February20,2018ª2018ElsevierInc.https://doi.org/10.1016/j.immuni.2017.12.013ImmunityArticleE3LigaseVHLPromotesGroup2InnateLymphoidCellMaturationandFunctionviaGlycolysisInhibitionandInductionofInterleukin-33ReceptorQianLi,1,3DuleiLi,1,3XianZhang,1,3QingqingWan,1WenZhang,1MingkeZheng,1LeZou,1ChrisElly,2JeeH.Lee,2andYun-CaiLiu1,2,4,*1InstituteforImmunology,Tsinghua-PekingCenterforLifeSciences,SchoolofMedicine,TsinghuaUniversity,Beijing100080,China2LaJollaInstituteforAllergyandImmunology,LaJolla,CA92037,USA3Theseauthorscontributedequally4LeadContact*Correspondence:yuncai_liu@mail.tsinghua.edu.cnhttps://doi.org/10.1016/j.immuni.2017.12.013SUMMARYGroup2innatelymphoidcells(ILC2s)areaspecial-izedsubsetoflymphoideffectorcellsthatarecriticallyinvolvedinallergicresponses;however,themecha-nismsoftheirregulationremainunclear.WereportthatconditionaldeletionoftheE3ubiquitinligaseVHLininnatelymphoidprogenitorsminimallyaffectedearly-stagebonemarrowILC2sbutcausedaselec-tiveandintrinsicdecreaseinmatureILC2numbersinperipheralnon-lymphoidtissues,resultinginreducedtype2immuneresponses.VHLdeficiencycausedtheaccumulationofhypoxia-induciblefactor1a(HIF1a)andattenu...
