Differential Effects of Peptidoglycan Recognition Proteins on Experimental Atopic and Contact Dermatitis Mediated by Treg and Th17 Cells 英文参考文献.docVIP

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Differential Effects of Peptidoglycan Recognition Proteins on Experimental Atopic and Contact Dermatitis Mediated by Treg and Th17 Cells 英文参考文献.doc

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Differential Effects of Peptidoglycan Recognition Proteins on Experimental Atopic and Contact Dermatitis Mediated by Treg and Th17 Cells 英文参考文献

DifferentialEffectsofPeptidoglycanRecognition ProteinsonExperimentalAtopicandContactDermatitis MediatedbyTregandTh17Cells ShinYongPark1,DipikaGupta1*,ChangH.Kim2,RomanDziarski1* 1IndianaUniversitySchoolofMedicine–Northwest,Gary,Indiana,UnitedStatesofAmerica,2SchoolofVeterinaryMedicine,PurdueUniversity,WestLafayette,Indiana, UnitedStatesofAmerica Abstract Skinprotectsthebodyfromtheenvironmentandisanimportantcomponentoftheinnateandadaptiveimmunesystems. Atopicdermatitisandcontactdermatitisareamongthemostfrequentinflammatoryskindiseasesandarebothdetermined bymultigenicpredisposition,environmentalfactors,andaberrantimmuneresponse.PeptidoglycanRecognitionProteins (Pglyrps) are expressed in the skin and we report here that they modulate sensitivity to experimentally-induced atopic dermatitis and contact dermatitis. Pglyrp32/2 and Pglyrp42/2 mice (but not Pglyrp22/2 mice) develop more severe oxazolone-induced atopic dermatitis than wild type (WT) mice. The common mechanism underlying this increased sensitivity of Pglyrp32/2 and Pglyrp42/2 mice to atopic dermatitis is reduced recruitment of Treg cells to the skin and enhanced production and activation Th17 cells in Pglyrp32/2 and Pglyrp42/2 mice, which results in more severe inflammationandkeratinocyteproliferation.ThismechanismissupportedbydecreasedinflammationinPglyrp32/2mice followinginvivoinductionofTregcellsbyvitaminDorafterneutralizationofIL-17.Bycontrast,Pglyrp12/2micedevelop less severe oxazolone-induced atopic dermatitis and also oxazolone-induced contact dermatitis than WT mice. Thus, Pglyrp3 and Pglyrp4 limit over-activation of Th17 cells by promoting accumulation of Treg cells at the site of chronic inflammation,whichprotectstheskinfromexaggeratedinflammatoryresponsetocellactivatorsandallergens,whereas Pglyrp1hasanoppositepro-inflammatoryeffectintheskin. Citation:ParkSY,GuptaD,KimCH,DziarskiR(2011)DifferentialEffectsofPeptidoglycanRecognitionProteinsonExperimentalAtopicandContactDermatitis MediatedbyTregandTh1