Progress in understanding postnatal immune dysregulation in allergic disease 英文参考文献.docVIP

Progress in understanding postnatal immune dysregulation in allergic disease 英文参考文献.doc

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Progress in understanding postnatal immune dysregulation in allergic disease 英文参考文献

INVITEDREVIEWARTICLE ProgressinUnderstandingPostnatalImmuneDysregulation inAllergicDisease SusanL.Prescott,MD,PhD,DavidMartino,BSc,MeganHodder,BSc,TaraRichman,BSc, andMeriK.Tulic,BSc,PhD INTRODUCTION hemodernerahasbeencharacterizedbyadramaticrise in susceptibility to a wide range of immune-mediated Abstract:Itisincreasinglyunlikelythatallergicdiseaseistheresultof T isolatedimmunedefects,butrathertheresultofalteredgeneactivation patterns in intricate immune networks. This appears to be driven by complex environmental changes, including microbial exposure, diet, and pollutants, which are known to modify immune development in earlylife,beginninginpregnancy.The?rstmodelsshowingpossible epigeneticmechanismsfortheseeffectsarebeginningtoemerge.This reviewfocusesonrecentadvancesinourknowledgeoftheconsequent effects on postnatal immune development, highlighting recognized differencesinchildrenwithandwithoutallergies.Althoughwechar- acterizedessentialdifferencesinlongitudinalT-celldevelopmentmore than10yearsago,newtechnologiesusingwholegenomemicroarrays arenowbeingusedtoexaminefordifferentialgeneexpressioninT cellsfromindividualswithallergies.Wehavealsorecentlyperformed the?rstcomprehensivestudyofthelongitudinaldevelopmentofinnate toll-likereceptorresponsesinchildrenwithandwithoutallergiesduring the ?rst 5 years of life, identifying signi?cant differences in these pathwaysaswell.Finally,althoughtherearepreliminarydifferencesin regulatoryT-cellfunctionatbirth,longitudinalstudiesarelimitedby dif?culties isolating these cells in suf?cient numbers from young childrenforfunctionalstudies.Thymictissueisolatedduringcardiac surgeryisarichsourceofregulatoryT-cellfunctioninchildrenand mayprovidefurtheravenuesforassessingdifferencesinmaturationof these cells in individuals with allergies. To further understand the pathogenesis of these altered patterns of immune response, future research needs to encompass the complexity of gene-environmental interactions, which confer individual susc

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