New dog and new tricks: evolving roles for IL‐33 in type 2 immunity

[摘要] IL‐33isamorerecentlyidentifiedmemberoftheIL‐1cytokinefamily,expressedinthenucleusofepithelialcellsandreleasedintotheextracellularspacefollowingtissuedamage.TheimpactofIL‐33asaregulatoroftheadaptiveimmuneresponsehasbeenstudiedextensively,withanunderstoodroleforIL‐33intheeffectorfunctionsofCD4+Th2cells.IL‐33,however,isnowbeingshowntoinitiatetheTh2‐polarizingfunctionofDCs,andstimulatethesecretionofthetype2‐associatedcytokines,IL‐4,IL‐5,andIL‐13,fromtissue‐residentinnate‐immunecells,especiallyILCsandMCs.IL‐33alsoinitiatesandperpetuateslocalinflammatoryresponsesthroughtherecruitmentandactivationoftype2‐andinflammatory‐associatedeffectors,suchaseosinophils,basophils,andneutrophils.Assuch,IL‐33drivesandamplifiestype2‐dependentimmunity,aswellastype2‐dependenttissuedestructionandinflammation.ItisalsobecomingapparentthatIL‐33supportsthereparativecapacityofmacrophageandILCs,butthesefunctionsmayalsocontributetochronicfibroticdiseases.Herein,wereviewnewdevelopmentsintheunderstandingofIL‐33asitfunctionsinTh2cellsandtype2immunity.ThisincludesadiscussionofourevolvingunderstandingofhowIL‐33directlyandindirectlypromotestype2immuneresponsesthroughactiononinnatecellsinimmunityandthepathogenesisofatopicandfibroticdiseases...

[学科分类] 生理学

[关键词] ST2;innate‐immune cells;immune response;fibrosis;T helper cells