Skin TLR7 Triggering Promotes Accumulation of Respiratory Dendritic Cells and Natural Killer Cells 英文参考文献.docVIP

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Skin TLR7 Triggering Promotes Accumulation of Respiratory Dendritic Cells and Natural Killer Cells 英文参考文献.doc

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Skin TLR7 Triggering Promotes Accumulation of Respiratory Dendritic Cells and Natural Killer Cells 英文参考文献

SkinTLR7TriggeringPromotesAccumulationof RespiratoryDendriticCellsandNaturalKillerCells HolgerHackstein1*,NicoleHagel1,AngelaKnoche1,SabineKranz1,Ju¨rgenLohmeyer2,Wernervon Wulffen3,OliviaKershaw4,AchimD.Gruber4,GregorBein1,NelliBaal1 1Institute for Clinical Immunology and Transfusion Medicine, Justus-Liebig-University Giessen, Member of the German Center for Lung Research, Giessen, Germany, 2Department ofInternal MedicineII, Giessen, Germany, 3Department ofInternal Medicine,V Pulmonary Diseases and ComprehensivePneumology Center, Klinikum Grosshadern,Ludwig-MaximiliansUniversity,Munich,Germany,4DepartmentofVeterinaryPathology,FreieUniversita¨t Berlin,Berlin,Germany Abstract TheTLR7agonistimiquimodhasbeenusedsuccessfullyasadjuvantforskintreatmentofvirus-associatedwartsandbasal cell carcinoma. The effects of skin TLR7 triggering on respiratory leukocyte populations are unknown. In a placebo- controlledexperimentalanimalstudywehaveusedmulticolourflowcytometrytosystematicallyanalyzethemodulationof respiratory leukocyte subsets after skin administration of imiquimod. Compared to placebo, skin administration of imiquimodsignificantlyincreasedrespiratorydendriticcells(DC)andnaturalkillercells,whereastotalrespiratoryleukocyte, alveolarmacrophages, classical CD4+ThelperandCD8+Tkiller cellnumbers werenotor onlymoderately affected.DC subpopulationanalysesrevealedthatelevationofrespiratoryDCwascausedbyanincreaseofrespiratorymonocyticDC andCD11bhiDCsubsets.Lymphocytesubpopulationanalysesindicatedamarkedelevationofrespiratorynaturalkillercells andasignificantreductionofBlymphocytes.Analysisofcytokineresponsesofrespiratoryleukocytesafterstimulationwith KlebsiellapneumoniaindicatedreducedIFN-candTNF-aexpressionandincreasedIL-10andIL-12p70productionafter7 daylowdoseskinTLR7triggering.Additionally,respiratoryNKcytotoxicactivitywasincreasedafter7dskinTLR7triggering. In contrast, lung histology and bronchoalveolar cell counts were not affected suggesting that skin TLR7 stim