AnnualReviewofImmunologyApoptosisandClearanceofApoptoticCellsShigekazuNagataLaboratoryofBiochemistryandImmunology,WorldPremierInternationalResearchCenterInitiativeImmunologyFrontierResearchCenter,OsakaUniversity,Osaka565–0871,Japan;email:snagata@ifrec.osaka-u.ac.jpAnnu.Rev.Immunol.2018.36:489–517FirstpublishedasaReviewinAdvanceonFebruary5,2018TheAnnualReviewofImmunologyisonlineatimmunol.annualreviews.orghttps://doi.org/10.1146/annurev-immunol-042617-053010Copyrightc⃝2018byAnnualReviews.AllrightsreservedKeywordsapoptosis,efferocytosis,macrophages,phosphatidylserine,flippase,scramblase,caspase,TIM4,TAMreceptorsAbstractThehumanbodygenerates10–100billioncellseveryday,andthesamenumberofcellsdietomaintainhomeostasisinourbody.Cellsinfectedbybacteriaorvirusesalsodie.Thecelldeaththatoccursunderphysiologicalconditionsmainlyproceedsbyapoptosis,whichisanoninflammatory,orsilent,process,whilepathogeninfectioninducesnecroptosisorpyropto-sis,whichactivatestheimmunesystemandcausesinflammation.Deadcellsgeneratedbyapoptosisarequicklyengulfedbymacrophagesfordegrada-tion.Caspasesarealargefamilyofcysteineproteasesthatactincascades.Acascadethatleadstocaspase3activationmediatesapoptosisandisrespon-sibleforkillingcells,recruitingmacrophages,andpresentingan“eatme”signal(s).Whenapoptoticcellsarenotefficientlyengulfedbymacrophages,theyundergosecondarynecrosisandreleaseintracellularmaterialsthatrep-resentadamage-associatedmolecularpattern,whichmayleadtoasystemiclupus-likeautoimmunedisease.489Clickheretoviewthisarticle'sonlinefeatures:•DownloadfiguresasPPTslides•Navigatelinkedreferences•Downloadcitations•Explorerelatedarticles•SearchkeywordsANNUALREVIEWSFurtherAnnu.Rev.Immunol.2018.36:489-517.Downloadedfromwww.annualreviews.orgAccessprovidedbyUniversityofCalifornia-SantaBarbaraon06/22/18.Forpersonaluseonly.INTRODUCTIONPeopledieforvariousreasons—aging,infection,accidents,organmalfunction,suicide.Weburyorcrematecorpsesswiftlytopreventthespreadofpathogens.Cells,too,dieforvariousreaso...
