Elevated Antigen-Driven IL-9 Responses Are Prominent in Peanut Allergic Humans 英文参考文献.docVIP

ElevatedAntigen-DrivenIL-9ResponsesAreProminent inPeanutAllergicHumans JungangXie1¤,LarisaC.Lotoski1,RishmaChooniedass2,Ruey-ChyiSu1,F.EstelleR.Simons1,2, JoelLiem3,AllanB.Becker1,2,JudeUzonna1,KentT.HayGlass1,2* 1Department of Immunology, University of Manitoba, Winnipeg, Canada, 2Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Canada, 3WindsorAllergyAsthmaEducationCentre,Ontario,Canada Abstract Food allergies, and peanut allergy in particular, are leading causes of anaphylactic fatalities worldwide. The immune mechanisms that underlie food allergy remain ill-defined and controversial, in part because studies in humans typically focusonanalysisofalimitednumberofprototypicalTh1/Th2cytokines.Herewedeterminethekineticsandprevalenceofa broad panel of peanut-driven cytokine and chemokine responses in humans with current peanut allergy vs those with stable, naturally occurring clinical tolerance to peanut. Our primary focus is identification of novel indicators of immune dysregulation. Antigen-specific cytokine mRNA and protein responses were elicited in primary culture via peanut or irrelevant antigen (Leishmania extract, milk antigens) mediated stimulation of fresh peripheral blood cells from 40 individuals.PeanutextractexposureinvitroinducedabroadpanelofresponsesassociatedwithTh2/Th9-like,Th1-likeand Th17-likeimmunity.Peanut-dependentType2cytokineresponseswerefrequentlyfoundinbothpeanutallergicindividuals and those who exhibit clinical tolerance to peanut ingestion. Among Th2/Th9-associated cytokines, IL-9 responses discriminated between allergic and clinically tolerant populations better than did commonly used IL-4, IL-5 or IL-13 responses. Comparison with responses evoked by unrelated control antigen-mediated stimulation showed that these differencesareantigen-dependentandallergen-specific.Conversely,theintensityofIL-12,IL-17,IL-23andIFN-cproduction wasindistinguishableinpeanutallergicandpeanuttolerantpopulations.Insummary,theabilityto