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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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