TheEntericNetwork:InteractionsbetweentheImmuneandNervousSystemsoftheGutBryanB.Yoo1,*andSarkisK.Mazmanian1,*1DivisionofBiology&BiologicalEngineering,CaliforniaInstituteofTechnology,Pasadena,California,91125,USASUMMARYInteractionsbetweenthenervousandimmunesystemsenabletheguttorespondtothevarietyofdietaryproductsthatitabsorbs,thebroadspectrumofpathogensthatitencounters,andthediversemicrobiomethatitharbors.Theentericnervoussystem(ENS)sensesandreactstothedynamicecosystemofthegastrointestinal(GI)tractbytranslatingchemicalcuesfromtheenvironmentintoneuronalimpulsesthatpropagatethroughoutthegut,andintootherorgansinthebodyincludingthecentralnervoussystem(CNS).ThisreviewwilldescribethecurrentunderstandingoftheanatomyandphysiologyoftheGItract,focusingontheENSandthemucosalimmunesystem.WehighlightemergingliteraturethattheENSisessentialforimportantaspectsofmicrobe-inducedimmuneresponsesinthegut.Whilemostbasicandappliedresearchinneurosciencehasfocusedonthebrain,theproximityoftheENStotheimmunesystemanditsinterfacewiththeexternalenvironmentsuggestthatnovelparadigmsfornervoussystemfunctionawaitdiscovery.eTOC/InBriefFollowingitsinitialdiscoveriesinthe1980sand1990s,arebirthinneuro-immunologyisemerginginthescientificliterature.Asknowledgeofthegastrointestinaltractexpands,includingitsneuronal,immunological,andmicrobialconstituents,inthisreview,MazmanianandYooprovidenewperspectivesandhypothesesregardingmucosalneuro-immunology.INTRODUCTIONThegastrointestinal(GI)tractspans5metersinlengthandhasanepithelialsurfaceareaof~32squaremeters(HelanderandFåndriks,2014).Itisthehometo70–80%ofthebody’simmunecells(Kagnoff,1987),over100millionneurons(Furnessetal.,2014),andupto100,000extrinsicnerveendings(GrundyandBrookes,2011).Themicrobiomeconsistsofasmanyas40trillioncellsandatleasthundredsofdifferentspecies(Lozuponeetal.,2012;Senderetal.,2016).AnimportantfunctionoftheGItractistosenseandrespondtoexternalcues.Diversecellularinteractionsareresponsibleforinterpretingthem,andthese*Correspondences:byoo@cal...
