First Insight into the Kinome of Human Regulatory T Cells 英文参考文献.docVIP

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First Insight into the Kinome of Human Regulatory T Cells 英文参考文献.doc

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First Insight into the Kinome of Human Regulatory T Cells 英文参考文献

FirstInsightintotheKinomeofHumanRegulatoryT Cells SebastianKo¨nig1,MichaelProbst-Kepper2,TobiasReinl3,AndreasJeron1,JochenHuehn3, BurkhartSchraven4,LotharJa¨nsch1* 1Department of Molecular Structural Biology, Helmholtz-Zentrum fu¨r Infektionsforschung, Braunschweig, Germany, 2Institute for Microbiology, Immunology and Hygiene,Sta¨dtisches KlinikumBraunschweiggGmbH,Braunschweig,Germany,3DepartmentofExperimentalImmunology,Helmholtz-Zentrumfu¨rInfektionsforschung, Germany,4InstituteofMolecularandClinicalImmunology,Otto-von-GuerickeUniversita¨t, Magdeburg,Germany Abstract RegulatoryTcells(Tregs)areessentialforcontrollingperipheraltolerancebytheactivesuppressionofvariousimmunecells including conventional T effector cells (Teffs). Downstream of the T cell receptor (TCR), more than 500 protein kinases encodedbythehumangenomehavetobeconsideredinsignalingcascadesregulatingtheactivationofTregsandTeffs, respectively.FollowingTCRengagement,Tregspossesanumberofuniqueattributes,suchasconstitutiveexpressionof Foxp3,hyporesponsivenessandpoorcytokineproduction.Furthermore,recentstudiesshowedthatalteredregulationof proteinkinasesisimportantforTregfunction.ThesedataindicatethatsignalingpathwaysinTregsaredistinctlyorganized andalterationsatthelevelofproteinkinasescontributetotheuniqueTregphenotype.However,kinase-basedsignaling networksinTregsarepoorlyunderstoodandnecessitatefurthersystematiccharacterization.Inthisstudy,weanalyzedthe differential expression of kinases in Tregs and Teffs by using a kinase-selective proteome strategy. In total, we revealed + quantitativeinformationon185kinasesexpressedinthehumanCD4 Tcellsubsets.Themajorityofkinaseswasequally abundant in both T cell subsets, but 11 kinases were differentially expressed in Tregs. Most strikingly, Tregs showed an alteredexpressionofcellcyclekinasesincludingCDK6.Quantitativeproteomicsgeneratesfirstcomparativeinsightintothe kinasecomplementsoftheCD4 TeffandTregsubset.Treg-specificexpressionpatternof11proteinkinase